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

What is a cure through gene therapy?:An analysis and evaluation of the use of “cure”

The development of gene therapy has always come with the expectation that it will offer a cure for various disorders, of which hemophilia is a paradigm example. However, although the term is used regularly, it is unclear what exactly is meant with “cure”. Therefore, the aim of this paper is to analyse how the concept of cure is used in practice and evaluate which of the interpretations is most suitable in discussions surrounding gene therapy. We analysed how cure is used in four different medical fields where the concept raises discussion. We show that cure can be used in three different ways: cure as normalization of the body, cure as obtaining a normal life, or cure as a change in identity. We argue that since cure is a practical term, its interpretation should be context-specific and the various uses can exist simultaneously, as long as their use is suitable to the function the notion of cure plays in each of the settings. We end by highlighting three different settings in the domain of hemophilia gene therapy in which the term cure is used and explore the function(s) it serves in each setting. We conclude that in the clinical application of gene therapy, it could be better to abandon the term cure, whereas more modest and specified definitions of cure are required in the context of health resource allocation decisions and decisions on research funding.</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

Ethics parallel research: An approach for (early) ethical guidance of biomedical innovation

Background: Our human societies and certainly also (bio) medicine are more and more permeated with technology. There seems to be an increasing awareness among bioethicists that an effective and comprehensive approach to ethically guide these emerging biomedical innovations into society is needed. Such an approach has not been spelled out yet for bioethics, while there are frequent calls for ethical guidance of biomedical innovation, also by biomedical researchers themselves. New and emerging biotechnologies require anticipation of possible effects and implications, meaning the scope is not evaluative after a technology has been fully developed or about hypothetical technologies, but real-time for a real biotechnology. Main text: In this paper we aim to substantiate and discuss six ingredients that we increasingly see adopted by ethicists and that together constitute "ethics parallel research". This approach allows to fulfil two aims: guiding the development process of technologies in biomedicine and providing input for the normative evaluation of such technologies. The six ingredients of ethics parallel research are: (1) disentangling wicked problems, (2) upstream or midstream ethical analysis, (3) ethics from within, (4) inclusion of empirical research, (5) public participation and (6) mapping societal impacts, including hard and soft impacts. We will draw on gene editing, organoid technology and artificial intelligence as examples to illustrate these six ingredients. Conclusion: Ethics parallel research brings together these ingredients to ethically analyse and proactively or parallel guide technological development. It widens the roles and judgements from the ethicist to a more anticipatory and constructively guiding role. Ethics parallel research is characterised by a constructive, rather than a purely critical perspective, it focusses on developing best-practices rather than outlining worst practice, and draws on insights from social sciences and philosophy of technology

Нарушение репродуктивной функции при простатите/синдроме хронической тазовой боли

Показано, что нелеченное хроническое воспаление предстательной железы приводит к нарушению показателей спермограммы и в ряде случаев к бесплодию при нормальном развитии половых желез и достаточном гормональном обеспечении организма. Бактерии, вирусы, лейкоциты, свободные радикалы, цитокины, иммунологические изменения и обструкция семявыводящих путей при простате являются кофакторами в развитии бесплодия.It is shown that untreated chronic inflammation of the prostate gland causes disturbances of spermogram count and strility in a number of cases at normal development of sex glands and sufficient hormone supply of the organism. Bacteria, viruses, leukocytes, free radicals, cytokines, immunological changes and obstruction of the deferent ducts in prostatitis are co−factors of sterility development

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

Should the 14‐day rule for embryo research become the 28‐day rule?

The “14‐day rule”—broadly construed—is used in science policy and regulation to limit research on human embryos to a maximum period of 14 days after their creation or to the equivalent stage of development that is normally attributed to a 14‐day‐old embryo (Hyun et al, 2016; Nuffield Council on Bioethics, 2017). For several decades, the 14‐day rule has been a shining example of how science policy and regulation can be developed with interdisciplinary consensus and applied across a number of countries to help fulfil an ethical and practical purpose: to facilitate efficient and ethical embryo research. However, advances in embryology and biomedical research have led to suggestions that the 14‐day rule is no longer adequate (Deglincerti et al, 2016; Shahbazi et al, 2016; Hurlbut et al, 2017). Therefore, should the 14‐day rule be extended and, if so, where should we draw a new line for permissible embryo research? Here, we provide scientific, regulatory and ethical arguments that the 14‐day rule should be extended to 28 days (or the developmental equivalent stage of a 28‐day‐old embryo)