Ectogestation ethics: The implications of artificially extending gestation for viability,newborn resuscitation and abortion

Recent animal research suggests that it may soon be possible to support the human fetus in an artificial uterine environment for part of a pregnancy. A technique of extending gestation in this way (“ectogestation”) could be offered to parents of extremely premature infants (EPIs) to improve outcomes for their child. The use of artificial uteruses for ectogestation could generate ethical questions because of the technology’s potential impact on the point of “viability”—loosely defined as the stage of pregnancy beyond which the fetus may survive external to the womb. Several medical decisions during the perinatal period are based on the gestation at which infants are considered viable, for example decisions about newborn resuscitation and abortion, and ectogestation has the potential to impact on these. Despite these possible implications, there is little existing evidence or analysis of how this technology would affect medical practice. In this paper, we combine empirical data with ethical analysis. We report a survey of 91 practicing Australian obstetricians and neonatologists; we aimed to assess their conceptual understanding of “viability,” and what ethical consequences they envisage arising from improved survival of EPIs. We also assess what the ethical implications of extending gestation should be for newborn and obstetric care. We analyze the concept of viability and argue that while ectogestation might have implications for the permissibility of neonatal life-prolonging treatment at extremely early gestation, it should not necessarily have implications for abortion policy. We compare our ethical findings with the results of the survey.     

Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10⁻⁵). The IL12RB2 gene (p-value: 2.18x10^-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.     

Putting placebo‐controlled trials in developing countries to the interpersonal justifiability test

This paper considers the ethics of placebo‐controlled trials in developing countries, where a treatment already exists but is not available due to the low local standard of care. Such trials would not be permitted in more developed nations where a higher standard of care is available. I argue that there are moral intuitions against such trials, but a further intuition that if the trials were aimed at producing treatment options for the developing world, that would be more permissible than if the trials were designed with the benefit of rich world people in mind. An approach based upon GA Cohen's work on interpersonal justifiability is suggested to allow us to explain these intuitions. Cohen's framework shows that these trials are ethically problematic because the inequality in healthcare provision between developing and developed nations that allows them to take place is at least partly the pharmaceutical corporations’ fault. Following Cohen's argument, this means the trials are non‐comprehensively justified. This allows for a more complete explanation of our intuitions than to consider such trials as cases of exploitation, because intuitions on the ethicacy of research can vary even when the exploitation relation remains the same. It is then established that there is good empirical evidence to believe that pharmaceutical corporations do fail the interpersonal justifiability test. The policy implications of this judgement are then considered, and it is suggested that the framework might be equally applicable to examining the permissibility of research conducted on vulnerable people within more developed nations.     

Ethical issues associated with HIV phylogenetics in HIV transmission dynamics research: A review of the literature using the Emanuel Framework

The reduced costs of DNA sequencing and the use of such data for HIV‐1 clinical management and phylogenetic analysis have led to a massive increase of HIV‐1 sequences in the last few years. Phylogenetic analysis has shed light on the origin, spread and characteristics of HIV‐1 epidemics and outbreaks. Phylogenetic analysis is now also being used to advance our knowledge of the drivers of HIV‐1 transmission in order to design effective interventions. However, HIV phylogenetic analysis presents unique ethical challenges, which have not been fully explored. This review presents an analysis of what appear to be key ethical issues in HIV phylogenetics in the hope of stimulating further conceptual and empirical work in this rapidly emerging area. We structure the review using the Emanuel Framework, a systematic, holistic framework, which has been adapted for use in developing countries, which bear the brunt of the HIV‐1 pandemic.     

Resource allocation for epidemic control over short time horizons

We present a model for allocation of epidemic control resources among a set of interventions. We assume that the epidemic is modeled by a general compartmental epidemic model, and that interventions change one or more of the parameters that describe the epidemic. Associated with each intervention is a 'production function' that relates the amount invested in the intervention to values of parameters in the epidemic model. The goal is to maximize quality-adjusted life years gained or the number of new infections averted over a fixed time horizon, subject to a budget constraint. Unlike previous models, our model allows for interacting populations and non-linear interacting production functions and does not require a long time horizon. We show that an analytical solution to the model may be difficult or impossible to derive, even for simple cases. Therefore, we derive a method of approximating the objective functions. We use the approximations to gain insight into the optimal resource allocation for three problem instances. We also develop heuristics for solving the general resource allocation problem. We present results of numerical studies using our approximations and heuristics. Finally, we discuss implications and applications of this work.     

Implementing shared decision making in routine mental health care

Shared decision making (SDM) in mental health care involves clinicians and patients working together to make decisions. The key elements of SDM have been identified, decision support tools have been developed, and SDM has been recommended in mental health at policy level. Yet implementation remains limited. Two justifications are typically advanced in support of SDM. The clinical justification is that SDM leads to improved outcome, yet the available empirical evidence base is inconclusive. The ethical justification is that SDM is a right, but clinicians need to balance the biomedical ethical principles of autonomy and justice with beneficence and non‐maleficence. It is argued that SDM is “polyvalent”, a sociological concept which describes an idea commanding superficial but not deep agreement between disparate stakeholders. Implementing SDM in routine mental health services is as much a cultural as a technical problem. Three challenges are identified: creating widespread access to high‐quality decision support tools; integrating SDM with other recovery‐supporting interventions; and responding to cultural changes as patients develop the normal expectations of citizenship. Two approaches which may inform responses in the mental health system to these cultural changes – social marketing and the hospitality industry – are identified.     

Health‐related Research Ethics and Social Value: Antibiotic Resistance Intervention Research and Pragmatic Risks

We consider the implications for the ethical evaluation of research programs of two fundamental changes in the revised research ethical guideline of the Council for International Organizations of Medical Sciences. The first is the extension of scope that follows from exchanging “biomedical” for “health‐related” research, and the second is the new evaluative basis of “social value,” which implies new ethical requirements of research. We use the example of antibiotic resistance interventions to explore the need to consider the instances of what we term the pragmatic risks of such interventions to evaluate the social value of certain kinds of health‐related research. These (pragmatic) risks severely threaten the social value of interventions in every area where human and social responses significantly impact on their effectiveness. Thus, the social value of health‐related research needed to demonstrate its effectiveness depends on the extent and successful management of such risks. Research designed to take into account the management of pragmatic risks also gives rise to similar types of risks, and the potential for social value in light of those risks needs to be considered in ethical reviews based on the new guidelines. We argue that, to handle this new expanded task, the international system of research ethical review addressed by the guidelines needs institutional development.     

‘Bioethical Realism’: A Framework for Implementing Universal Research Ethics

Implementation of existing ethical guidelines for international collaborative medical and health research is still largely controversial in sub‐Saharan Africa for two major reasons: One, they are seen as foreign and allegedly inconsistent with what has been described as an ‘African worldview’, hence, demand for their strict implementations reeks of ‘bioethical imperialism’. Two, they have other discernible inadequacies – lack of sufficient detail, apparent as well as real ambiguities, vagueness and contradictions. Similar charges exist(ed) in other non‐Western societies. Consequently, these guidelines have been correctly judged as an inadequate response to the complex and ever shifting dilemmas met by researchers and research regulators in the field. This paper proposes a framework for effective implementation of existing guidelines without much worry about bioethical imperialism and other inadequacies. This framework is proposed using an analogy of Legal Realism, specifically its key assertions on how, in reality, judicial systems operate using general legal rules to settle specific cases. Legal realists assert that in judicial decision‐making, general legal rules do not totally dictate court decisions in specific cases. This analogy is used to coin a new term, ‘Bioethical Realism.’ The framework suggests that local Research Ethics Committees ought to be construed as analogues of judicial courts with the resulting implications. Consequently, just like legal rules are general rules that do not always dictate court decisions, similarly international bioethical guidelines are general ethical rules that should not always dictate local RECs’ decisions and such decisions (ought to) enjoy considerable immunity from outsiders.     

Insight and the no‐self in deep brain stimulation

Ethical analyses of the effects of neural interventions commonly focus on changes to personality and behavior, interpreting these changes in terms of authenticity and identity. These phenomena have led to debate among ethicists about the meaning of these terms for ethical analysis of such interventions. While these theoretical approaches have different criteria for ethical significance, they agree that patients’ reports are concerning because a sense of self is valuable. In this paper, I question this assumption. I propose that the Buddhist theory of no‐self offers a novel approach to making ethical sense of patients’ claims following deep brain stimulation. This alternative approach is based on the value of insight into patterns of cause and effect among mental states and actions.     

Moral residue and health justice for the global south: Addressing past issues through current interventions and research

This paper introduces the concept of moral residue to global health, and shows how its presence undermines crucial interventions and research, especially in the global south. Lingering feelings of anxiety, anger, blame or frustration often exist among local populations, where previous interventions or research have left traces of harm and/or exploitation. The existence of such feelings reflects the presence of moral residue, recognizing the moral experiences of epistemic injustices, which in turn undermines critical interventions and research through outright rejection or passive non‐compliance among affected populations. While such situations have been variously interpreted and relevant strategies developed to address the issues, little to no consideration is made on the implications of moral residue experiences in global health contexts and how to address them. This paper demonstrates the presence of moral residue in global health and proffers an African ethical approach, a harmony framework, for addressing moral residue issues, as part of a holistic approach towards tackling population health crises without compromising health gains for affected populations in the global south.     

EXISTENCE: WHO NEEDS IT? THE NON‐IDENTITY PROBLEM AND MERELY POSSIBLE PEOPLE

In formulating procreative principles, it makes sense to begin by thinking about whose interests ought to matter to us. Obviously, we care about those who exist. Less obviously, but still uncontroversially, we care about those who will exist. Ought we to care about those who might possibly, but will not actually, exist? Recently, unusual positions have been taken regarding merely possible people and the non‐identity problem. David Velleman argues that what might have happened to you – an existent person – often doesn't merit moral consideration since the alternative person one would have been had what might have happened actually happened is a merely possible person about whom one has no reason to care. He argues that his way of thinking can eliminate the non‐identity problem. Caspar Hare argues that merely possible people have interests and are morally relevant. He argues that we can solve the non‐identity problem by rejecting the view that merely possible people are morally irrelevant. Both Hare and Velleman argue that focusing on one's de dicto rather than on one's de re children can help us avoid the non‐identity problem. I analyze the role that merely possible, nonexistent hypothetical entities ought to play in our moral reasoning, especially with regard to procreation. I refute both Velleman's and Hare's views and demonstrate the difficulties we encounter when we try to apply their views to common non‐identity cases. I conclude with the common‐sense view regarding who matters, morally: only those who do, did, or will exist.     

Addressing the challenge for expedient ethical review of research in disasters and disease outbreaks

Guideline 20 of the updated International Ethics Guidelines for Health‐related Research Involving Humans (2016) by the Council for International Organizations of Medical Sciences (CIOMS) provides guidance on research in disasters and disease outbreaks against the background of the need to generate knowledge quickly, overcome practical impediments to implementing such research, and the need to maintain public trust. The guideline recommends that research ethics committees could pre‐screen study protocols to expedite ethical reviews in a situation of crisis, that pre‐arrangements be made regarding data sharing and biomedical sample sharing, and that sponsors and research ethics committees seek to minimize risk to researchers conducting research during a disaster. This paper critiques these recommendations against the background of the findings of a survey of public health officials and chairs of research ethics committees in the Caribbean during 2016, which sought to determine the best template for the expeditious ethical review of research proposals in emergency and epidemic situations in the Caribbean, and whose findings can serve as a model for other low‐ and middle‐income countries.     

German law on circumcision and its debate: How an ethical and legal issue turned political

The article aims to illuminate the recent debate in Germany about the legitimacy of circumcision for religious reasons. The aim is both to evaluate the new German law allowing religious circumcision, and to outline the resulting conflict between the surrounding ethical and legal issues. We first elucidate the diversity of legal and medical views on religious circumcision in Germany. Next we examine to what extent invasive and irreversible physical interventions on infant boys unable to given their consent should be carried out for non‐medical reasons. To this end, the potential benefits and harms of circumcision for non‐medical reasons are compared. We argue that circumcision does not provide any benefits for the ‘child as a child’ and poses only risks to boys. We then set out to clarify and analyse political (rather than ethical) justifications of the new circumcision law. We demonstrate through this analysis how the circumcision debate in Germany has been transformed from a legal and ethical problem into a political issue, due at least in part to Germany's unique historical context. Although such a particular political sensibility is entirely comprehensible, it raises particular problems when it comes to framing and responding to medical ethical issues – as in the case of religious circumcision.     

Reflections on research ethics in a public health emergency: Experiences of Brazilian women affected by Zika

In Brazil, the epicenter of the Zika crisis, brown, black, and indigenous poor women living in municipalities with scarce resources were disproportionally affected. The gendered consequences of the epidemic exposed how intersectional lenses are central to understand the impact of public health emergencies in the lives of women and girls. The demand for Zika-affected children and women to be research participants is relevant for an ethical analysis of participant protection procedures during a crisis. We investigated how women experienced research participation by analyzing their narratives. Two-year-long longitudinal qualitative study in Brazilian sites located in the epidemic's epicenter was performed using mixed methods: ethnography with women from two distinct states and individual semi-structured interviews with five women in different Zika-affected states, four of which were community leaders. All women in the study were mothers or grandmothers of Zika-affected children. Thematic analysis was used for data evaluation. Women perceived being pressured to participate in research and a lack of benefit sharing. Structural determinants of gender inequality, such as its effect on power distribution, were found to impact research participant protection. Formal procedures for research protocols approvals were insufficient in protecting participants because these instruments were unable to account for structural aspects. Communitarian mobilization, through WhatsApp groups, was found to be an important mechanism to create conditions to challenge oppressive structures. Strengthening public health, effective community-based participation in research planning and implantation of ethical strategies that promotes gender equality can have transformative effect on unequal power structures and promote participant protection.     

Incentivizing Patient Choices: The Ethics of Inclusive Shared Savings

Is it ethical to pay patients for selecting cheaper medical treatments? The healthcare system in the United States is notoriously profligate, at least in part because when insurers foot the bill, patients have little incentive to avoid wasteful treatments. One familiar means for dealing with this problem is for insurers to offer reduced co‐pays to patients who select cheaper treatments. Would it be ethical to take this one step further, beyond the zero bound, sharing the savings of cheaper treatments by positively paying the patients who select them? Schmidt & Emanuel recently proposed this policy of ‘Inclusive Shared Savings’ (ISS). This article examines various ethical objections to the idea.     

The use of Ethics Decision‐Making Frameworks by Canadian Ethics Consultants: A Qualitative Study

In this study, Canadian healthcare ethics consultants describe their use of ethics decision‐making frameworks. Our research finds that ethics consultants in Canada use multi‐purpose ethics decision‐making frameworks, as well as targeted frameworks that focus on reaching an ethical resolution to a particular healthcare issue, such as adverse event reporting, or difficult triage scenarios. Several interviewees mention the influence that the accreditation process in Canadian healthcare organizations has on the adoption and use of such frameworks. Some of the ethics consultants we interviewed also report on their reluctance to use these tools. Limited empirical work has been done previously on the use of ethics decision‐making frameworks. This study begins to fill this gap in our understanding of the work of healthcare ethics consultants.     

No ethical divide between China and the West in human embryo research

This is a discussion of the reaction to the recent research article publication in the journal Protein & Cell by a group of scientists at Sun Yat‐sen University using the CRISPR/Cas9 technique on editing non‐viable human zygotes. Many commentators condemned the Chinese scientists for overstepping ethical boundaries long accepted in Western countries and accused China of having lax regulations on genomic research in general. We argue that not only did this research follow strict ethical standards and fully comply with current regulations, but China also has a well‐developed regulatory framework governing such research comparable to many developed countries. We see the reactions among Western commentators as a misunderstanding of the current situation and an expression of a lack of willingness to acknowledge China as an equal partner in the international debate about proper limits to the development of new biotechnologies.     

Survey on Ethical Conduct Thresholds in Cardiologal Medical Practice in Argentina

The purpose of this study was to analyze the attitude of a group of cardiologists on the ethical conducts they would accept or adopt when encountered with different hypothetical situations of medical practice. Between August and September of 2011, 700 Argentine cardiologists were surveyed in situations which posed ethical dilemmas in the patient‐physician relationship, among colleagues or involving financial agreements with employers or the pharmaceutical industry. Ethical conflicts were evidenced in a series of inappropriate conducts such as differential fees, trips and meals sponsored by laboratories, splitting fees, overbilling, self‐referral, charging for patient referral, financial compensation for ordering medical procedures, and various situations derived from the relationship with employers. In general, financial compensation from the pharmaceutical industry was more accepted than the conflictive situations which directly involved patients, colleagues or employers. The rejection of these conducts, the physicians' deontological education and the improvement of financial and organizational conditions in medical practice will help to encourage better medical professionalism and avoid unseemly behaviors.     

A Costly Separation Between Withdrawing and Withholding Treatment in Intensive Care

Ethical analyses, professional guidelines and legal decisions support the equivalence thesis for life‐sustaining treatment: if it is ethical to withhold treatment, it would be ethical to withdraw the same treatment. In this paper we explore reasons why the majority of medical professionals disagree with the conclusions of ethical analysis. Resource allocation is considered by clinicians to be a legitimate reason to withhold but not to withdraw intensive care treatment. We analyse five arguments in favour of non‐equivalence, and find only relatively weak reasons to restrict rationing to withholding treatment. On the contrary, resource allocation provides a strong argument in favour of equivalence: non‐equivalence causes preventable death in critically ill patients. We outline two proposals for increasing equivalence in practice: (1) reduction of the mortality threshold for treatment withdrawal, (2) time‐limited trials of intensive care. These strategies would help to move practice towards more rational treatment limitation decisions.     

Should human germ line editing be allowed? Some suggestions on the basis of the existing regulatory framework

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense at all, because the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non‐sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose.