Ethics of modifying the mitochondrial genome

Recent preclinical studies have shown the feasibility of specific variants of nuclear transfer to prevent mitochondrial DNA disorders. Nuclear transfer could be a valuable reproductive option for carriers of mitochondrial mutations. A clinical application of nuclear transfer, however, would entail germ-line modification, more specifically a germ-line modification of the mitochondrial genome. One of the most prominent objections against germ-line modification is the fear that it would become possible to alter 'essential characteristics' of a future person, thereby possibly violating the child's right to an open future. As only the nuclear DNA would contain the ingredients for individual characteristics, modification of the mtDNA is often considered less controversial than modification of the nuclear DNA. This paper discusses the tenability of this dichotomy. After having clarified the concept of germ-line modification, it argues that modification of the mtDNA is not substantively different from modification of the nuclear DNA in terms of its effects on the identity of the future person. Subsequently the paper assesses how this conclusion affects the moral evaluation of nuclear transfer to prevent mtDNA disorders. It concludes that the moral acceptability of germ-line modification does not depend on whether it alters the identity of the future child-all germ-line modifications do-but on whether it safeguards the child's right to an open future. If nuclear transfer to prevent mtDNA disorders becomes safe and effective, then dismissing it because it involves germ-line modification is unjustified

Simulation study of lightning fault waveforms influenced by the arc quenching properties of wooden distribution line poles

Abstract With an ever increasing emphasis on reliability of supply, improvement in the lightning performance of distribution lines is required. The arc quenching properties of wooden distribution line poles during lightning strikes are an important factor in the reduction of switchgear operation, hence outages. Measurements were conducted on a 22 kV distribution line and it was suspected, in some cases, that direct lightning strikes to the line did not cause switchgear operation. Distribution lines predominantly use wooden poles with a specific configuration which incorporates a 'wooden' spark gap. This paper provides background to the basic configuration of a typical distribution line and the processes which govern the electric arc. A simulation using a dynamic arc model shows that field measured lightning overvoltages on a distribution line are reproducible through system modelling. The simplistic dynamic arc model developed is sufficiently accurate to describe a set of arcs in a larger system such as a distribution line

Pathogens of common wasps in their native and invaded range.

The clinical introduction of novel medical devices often occurs without evidence of good methodological quality and with relatively little oversight and regulation. As a consequence, the safety, efficacy, and long-term effects of devices are frequently insufficiently known upon device approval. Recent controversies surrounding the Poly Implant Prothese (PIP) breast implants, metal-on-metal hip implants, and interspinous implants underscore the need to reconsider how innovation in medical devices can adhere to sound ethical standards without inhibiting surgical research and development. In this article, the introduction of spinal implants is taken as an example to firstly discuss the scientific and ethical challenges of developing, testing, and introducing novel medical devices and to secondly identify avenues for improving the existing regulatory frameworks for such innovation. Two measures for improvement are most feasible in the short term: demanding prospective studies before device introduction and developing registries to monitor and evaluate new medical devices. LEVEL OF EVIDENCE: 5

The unique status of first-in-human studies: strengthening the social value requirement

For clinical research to be ethical, risks need to be balanced by anticipated benefits. This is challenging for first-in-human (FIH) studies as participants are not expected to benefit directly, and risks are potentially high. We argue that this differentiates FIH studies from other clinical trials to the extent that they should be given unique status in international research ethics guidelines. As there is a general positive attitude regarding the benefits of science, it is important to establish a more systematic method to assess anticipated social value to safeguard participants not only from enrolling in risky, but also in futile trials. Here, we provide some of necessary steps needed to assess the anticipated social value of the intervention

Nature-versus-nurture considered harmful:Actionability as an alternative tool for understanding the exposome from an ethical perspective

Exposome research is put forward as a major tool for solving the nature-versus-nurture debate because the exposome is said to represent “the nature of nurture.” Against this influential idea, we argue that the adoption of the nature-versus-nurture debate into the exposome research program is a mistake that needs to be undone to allow for a proper bioethical assessment of exposome research. We first argue that this adoption is originally based on an equivocation between the traditional nature-versus-nurture debate and a debate about disease prediction/etiology. Second, due to this mistake, exposome research is pushed to adopt a limited conception of agential control that is harmful to one's thinking about the good that exposome research can do for human health and wellbeing. To fully excise the nature-versus-nurture debate from exposome research, we argue that exposome researchers and bioethicists need to think about the exposome afresh from the perspective of actionability. We define the concept of actionability and related concepts and show how these can be used to analyze the ethical aspects of the exposome. In particular, we focus on refuting the popular “gun analogy” in exposome research, returning results to study participants and risk-taking in the context of a well-lived life.</p

Nature-versus-nurture considered harmful:Actionability as an alternative tool for understanding the exposome from an ethical perspective

Exposome research is put forward as a major tool for solving the nature-versus-nurture debate because the exposome is said to represent “the nature of nurture.” Against this influential idea, we argue that the adoption of the nature-versus-nurture debate into the exposome research program is a mistake that needs to be undone to allow for a proper bioethical assessment of exposome research. We first argue that this adoption is originally based on an equivocation between the traditional nature-versus-nurture debate and a debate about disease prediction/etiology. Second, due to this mistake, exposome research is pushed to adopt a limited conception of agential control that is harmful to one's thinking about the good that exposome research can do for human health and wellbeing. To fully excise the nature-versus-nurture debate from exposome research, we argue that exposome researchers and bioethicists need to think about the exposome afresh from the perspective of actionability. We define the concept of actionability and related concepts and show how these can be used to analyze the ethical aspects of the exposome. In particular, we focus on refuting the popular “gun analogy” in exposome research, returning results to study participants and risk-taking in the context of a well-lived life.</p

Governing Gene Drive Technologies:A Qualitative Interview Study

Background: Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth. Methods: A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically. Results: Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment. Conclusions: The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations

Mitochondrial Replacement Techniques:Remaining Ethical Challenges

Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance

How to fulfill the expert role in public dialogue:The Dutch dialogue on human germline genetic modification as a case

Over the last decades science communication theory appears to have evolved at a much faster pace than science communication practice. Scientists seem willing to step into the public domain, but a genuine two-way interaction with the public is only rarely observed. We argue that part of this discrepancy between theory and practice may actually be caused by the lacking of a clear description of the modern expert role; the role a scientist should take in contemporary science communication. In this contribution we use an example of good practice—the Dutch dialogue on human germline genetic modification—to inform theory. We analyse guiding principles for the design and execution of this dialogue and observe expert behavior in three separate dialogue sessions. With the combined findings, we present a detailed description of the modern expert role in terms of three responsibilities, with for each responsibility three prompts for behavior. For the responsibility to share these are to select expert knowledge that is relevant to the goal; to present expert knowledge in a meaningful and accessible language; and to be cautious in sharing personal considerations. For the responsibility to listen and learn these are to consider interactions with members of the public as opportunities to learn; to be patient and supportive; and to assist in stimulating in-depth dialogue. For the responsibility to invest in relationships these are to assist in creating an ambiance of safety and relevance; to preserve trust; and to convey respect for every contribution and every point of view. Each behavioral prompt is further concretized with concomitant actions and practice examples as collected from observing experts in action. The implications for scientists engaging in contemporary science communication, as well as for science communication trainers, are discussed.</p