Karla Karoline Sonne Kalinka Alex

Definition of problem Newborn screening (NBS) is an internationally successful program for the secondary prevention of rare congenital diseases. At present, most of the target conditions in NBS are diagnosed by biochemical markers. Recent advances in genomic sequencing and in the bioinformatic evaluation of genetic variants will soon make it feasible however to expand NBS significantly by testing newborns directly for pathogenic variants. Yet, genomic newborn screening (gNBS) raises important ethical issues that require resolution, given that several pilot studies on gNBS implementation are already underway. Given a rapidly growing scholarly engagement with the ethics of gNBS, a more systematic and comprehensive mapping of the ethical issues and considerations relevant to gNBS is needed to move the debate forward at this point. Methods In this integrative review, we survey the literature with the aim of delineating a conceptual framework for the ethics of gNBS, which organizes the ongoing debate and thereby provides guidance for further research. Here in Part II, we outline a tentative normative framework for the ethics of gNBS by systematizing the core ethical principles advanced in the literature and offer an original contribution to the debate beyond a mere survey of considerations by proposing a substantive interpretation of these principles and how they relate to each other in the gNBS context. We demonstrate the general utility of this framework for addressing the ethical issues involved in gNBS program design by drawing out its implications for some of the issues presented in Part I. Conclusion In Part I, we formulated a requirement of informed consent for gNBS. Since newborns still lack a capacity for autonomous choice and informed consent, we approach gNBS program design through the question of what renders it ethically permissible for the child’s custodians to consent to gNBS in its name. Consequently, we discuss the authority of parents as surrogate decision-makers for their child, who are bound by a duty of care towards it. We substantiate this duty (a) by discussing several rights of the child, viz., its rights to informational self-determination, genetic ignorance, privacy, and an open future, and (b) by developing a specification of the best interest standard for children as the main principle that should guide and constrain both parental decision-making and gNBS program design. Finally, we consider concerns that gNBS could result in a harmful medicalization of healthy children.

Definition of problem Newborn screening (NBS) is an internationally successful program for the secondary prevention of rare congenital diseases. At present, most of the target conditions in NBS are diagnosed by biochemical markers. Recent advances in genomic sequencing and in the bioinformatic evaluation of genetic variants will soon make it feasible however to expand NBS significantly by testing newborns directly for pathogenic variants. Yet, genomic newborn screening (gNBS) raises important ethical issues that require resolution, given that several pilot studies on gNBS implementation are already underway. Given a rapidly growing scholarly engagement with the ethics of gNBS, a more systematic and comprehensive mapping of the ethical issues and considerations relevant to gNBS is needed to move the debate forward at this point. - Methods In this integrative review, we survey the literature with the aim of delineating a conceptual framework for the ethics of gNBS, which organizes the ongoing debate and thereby provides guidance for further research. Here in Part I, we focus primarily on an exposition of the ethical issues and questions involved in gNBS program design. - Conclusion The ethical issues divide into issues regarding (1) the test itself and the selection of target conditions, (2) informed consent, and (3) genomic data generation, storage, and use. Regarding (1) we discuss several dimensions along which potential target conditions can differ and their ethical implications, and formulate some requirements on appropriate selection criteria with special regard to minimizing diagnostic and therapeutic uncertainty. Regarding (2) we discuss the need for informed consent, the structure and content of pre-test counseling (when, who, what, how), the suggestion of a tiered testing offer, and familial conflict. Regarding (3) we discuss liberal versus restrictive approaches to genomic data generation, parental consent to genomic raw data storage for further uses beyond the test, some candidate further uses, and the risk of abuse.

[English version below] Diese Stellungnahme zielt darauf ab, Empfehlungen für akzeptable Rahmenbedingungen eines Genomischen-Neugeborenen-Screening (gNBS)-Programms in Deutschland zu formulieren, darunter Empfehlungen zu Auswahlkriterien für Zielkrankheiten und zum Management eines gNBS-Programms sowie zur gesetzlichen Neuregulierung. Sie ist Ergebnis eines dreijährigen Forschungsprojektes, das an den Universitäten Heidelberg und Mannheim durchgeführt wurde. An dem interdisziplinären Projekt beteiligt waren Forscher:innen aus den Bereichen Kinder- und Jugendmedizin, Humangenetik, Rechtswissenschaft, Medizinische Psychologie und Medizinethik sowie Vertreter:innen von Patient:innen-Organisationen (Kindernetzwerk e.V. und Deutsche Interessengemeinschaft Phenylketonurie und verwandte angeborene Stoffwechselstörungen e.V.). Das Projekt wurde vom Bundesministerium für Bildung und Forschung (BMBF; seit 2025 Bundesministerium für Forschung, Technologie und Raumfahrt: BMFTR) gefördert und trägt den Titel NEW_LIVES („Genomic NEWborn screening programs – Legal Implications, Value, Ethics and Society” – „Genomische Neugeborenen-Screening-Programme – Rechtliche Implikationen, Werte, Ethik und Gesellschaft“). Die Stellungnahme beginnt mit einführenden Kapiteln zum Hintergrund des gNBS aus Sicht der verschiedenen Fachbereiche und aus Sicht der Gesellschaft, gefolgt von konkreten Empfehlungen für ein zukünftig mögliches gNBS-Pro- gramm in Deutschland. In der Einleitung (1.) werden erste Ergebnisse bisheriger Forschungsprojekte zum gNBS zusammengefasst und die Zielsetzung und Methode, einschließlich der Rolle von Patient:innen-Vertreter:innen bei der Erarbeitung der Stellungnahme werden beschrieben. In Abschnitt 2 („Medizinischer Hintergrund“) werden Entwicklung, Umfang und Ablauf des derzeitigen Neugeborenen-Screening (NBS)-Programms in Deutschland beschrieben und die Besonderheiten eines gNBS-Programms erläutert. Abschnitt 3 („Perspektive von Patient:innen, Eltern und medizinischem Personal“) fasst die Ergebnisse der sozialempirischen Studien zusammen, die im Rahmen des Projektes NEW_LIVES durchgeführt wurden (Fokusgruppen, bevölkerungs-repräsentative Befragung, querschnittliche Online-Befragung) und vergleicht die Ergebnisse mit anderen, internationalen Studien. Abschnitt 3 enthält außerdem eine gemeinsame Stellungnahme der beiden Patient:innen-Organisationen, die am Projekt NEW_LIVES mitgewirkt haben, zum gNBS. Abschnitt 4 („Genomisches Neugeborenen-Screening aus rechtlicher Sicht“) skizziert den rechtlichen Regulierungsrahmen zum gNBS in Deutschland. Abschnitt 5 („Genomisches Neugeborenen-Screening aus ethischer Sicht“) benennt zentrale ethische Herausforderungen des gNBS und formuliert ethische Orientierungsmaßstäbe für ein zukünftiges gNBS-Programm in Deutschland. Da die Neugeborenen diejenigen sind, die an einem gNBS teilnehmen würden und davon profitieren könnten, stellt deren Kindeswohl den zentralen ethischen Orientierungsmaßstab für die Bewertung dar. Die sich in Abschnitt 6 anschließenden Empfehlungen sind aus Sicht aller an der Erarbeitung dieser Stellungnahme beteiligten Fachdisziplinen und der Patient:innen-Organisationen verfasst Darunter sind einerseits transparente Auswahlkriterien für Zielkrankheiten eines gNBS-Programms (Kriterien 1–11). Andererseits werden Empfehlungen für die Einführung, Qualitätssicherung und Nutzenbewertung eines gNBS-Programms formuliert (Kriterien 12–18). Zudem enthält diese Stellungnahme Empfehlungen zur gesetzlichen Neuregulierung. Eine Publikation der Empfehlungen auf Englisch findet sich in Schnabel-Besson et al.: “A multi-dimensional fra- mework for establishing and managing a genomic newborn screening program” (Arbeitstitel; zum Zeitpunkt des Verfassens dieser Stellungnahme in Vorbereitung; DOI der Preprint-Version: 10.1101/2025.06.17.25329 471). - This position paper has the aim of formulating recommendations for what would be an acceptable framework for a genomic newborn screening (gNBS) programme in Germany, including recommendations for selection criteria for target diseases, and for the management of a gNBS programme, as well as for revision of legislation. It is the result of a research project conducted at the Universities of Heidelberg and Mannheim over the course of three years. This interdisciplinary project brought together researchers from the fields of paediatrics and adolescent medicine, human genetics, law, medical psychology, and medical ethics, as well as representatives of patient organisations (Kindernetzwerk e.V., and Deutsche Interessenge- meinschaft Phenylketonurie und verwandte angeborene Stoffwechselstörungen e.V.). The project was funded by the German Federal Ministry of Education and Research (BMBF; since 2025 Federal Ministry of Research, Technology and Space: BMFTR) and is called NEW_LIVES (“Genomic NEWborn screening programs – Legal Implications, Value, Ethics and Society”). The position paper begins with introductory chapters on gNBS from the perspective of the different disciplines, and from a societal viewpoint, followed by concrete recommendations for a possible future gNBS programme in Germany. The Introduction (1.) summarises the initial results of previous research projects on gNBS, and describes the objectives, and methodology, including the role of patient representatives, in the development of the position paper. Section 2 (“Medical Background”) describes the development, scope, and process of the current NBS programme in Germany, and explains the specific features of a gNBS programme. Section 3 (“Perspectives of Patients, Parents, and Medical Staff”) summarizes the results of the social-empirical studies conducted as part of the NEW_LIVES project (focus groups, population-representative survey, cross-sectional online survey), and compares the results with other, international studies. Section 3 also contains a joint statement on gNBS by the two patient organisations that participated in the NEW_LIVES project. Section 4 (“Genomic Newborn Screening from a Legal Perspective”) outlines the legal regulatory framework for gNBS in Germany. Section 5 (“Genomic Newborn Screening from an Ethical Perspective”) identifies key ethical challenges of gNBS, and formulates ethical guidelines for a future gNBS programme in Germany. Since newborns are the ones who would participate in, and benefit from gNBS, their welfare represents the central ethical guideline for the evaluation. The recommendations in Section 6 are written from the perspective of all disciplines, and patient organisations involved in the development of this position paper. These recommendations reflect the consensus of the inter-, and transdisciplinary group of authors, and form the core of the position paper. They comprise 18 criteria for a possible future gNBS programme in Germany. These include, on the one hand, transparent selection criteria for target diseases of a gNBS programme (criteria 1–11). On the other hand, recommendations are formulated for the introduction, quality assurance, and benefit assessment of a gNBS programme (criteria 12–18). This position paper also contains recommendations for new legal regulations. An English version of the recommendations, including the 11 criteria for selecting target diseases and the 7 criteria for programme management can be found in Schnabel-Besson E, Dikow N, Alex K et al.: “A multidimensional framework for establishing and managing a genomic newborn screening program” (working title; in preparation at the time of writing this position paper; doi of preprint version: 10.1101/2025.06.17.25329471).

The advancement of genome sequencing technology and its potential application in newborn screening is being discussed in various countries. Genomic newborn screening (gNBS) can provide parents with information about their child's genetic susceptibility for known disorders. However, it also presents ethical and psychosocial challenges. This study was carried out with a view toward the possible introduction of gNBS in Germany. Due to the existing challenges, it is crucial to understand different perspectives of relevant groups in Germany before implementing gNBS. Four online focus groups were conducted with parents, patient representatives, and healthcare professionals to explore perceived opportunities and challenges, as well as needs regarding a potential gNBS program. Discussions with altogether 24 participants were semi-structured using a pre-defined interview guide. Sessions were audio-visually recorded and transcripts were analyzed using a structuring qualitative content analysis combining both deductive and inductive methods. Participants expressed positive views about gNBS but also reservations about a gNBS program and posed requirements for operating conditions. One salient theme that emerged was hope for certainty through gNBS in the face of numerous uncertainties. The study complements the perspective of patient representatives, providing further insight into the subject matter. This is a valuable contribution as they possess a comprehensive understanding of the medical, psychological, and ethical considerations involved. Patient representatives placed particular emphasis on the advantages of avoiding a diagnostic odyssey and the significance of support systems. The results provide first insights into different views on gNBS in Germany. These views can inform the potential preparation of a gNBS program in Germany, particularly with regard to information and consent requirements. Implications for practice, such as informing and educating parents about gNBS during pregnancy, can be derived from the study. WHAT IS KNOWN ABOUT THIS TOPIC: Previous studies have indicated that there is significant public and—more particularly parental—interest in genomic newborn screening (gNBS). However, discrepancies exist regarding preferences for the scope of reported results, including differences between the views of healthcare professionals, parents, and the public. WHAT THIS PAPER ADDS TO THE TOPIC: This study offers insights into various perspectives on the potential implementation of gNBS in Germany, highlighting divergent views of healthcare professionals and parents, while also introducing a novel and valuable contribution by including the viewpoints of patient representatives.

Foreword The following guideline emerged from the project DUMFE: Dual Use and Misuse of Research Results (“Dual use und Missbrauch von Forschungsergebnissen”), funded by the German Federal Ministry of Education and Research (BMBF, 01GP2187). In recent years, dual use has become a significant issue in research ethics for numerous reasons, garnering considerable attention not only within the ethical community but also in the broader scientific community and among political and security circles. Among the reasons for this attention are the dissemination of scientific developments with high misuse potential, such as gain-of-function experiments (Imai et al. 2012; Herfst et al. 2012; Imperiale and Casadevall 2018); political factors, including recent shifts in the global security landscape (Nationale Akademie der Wissenschaften Leopoldina (Leopoldina) and Deutsche Forschungsgemeinschaft (DFG) 2024, 9ff.); and heightened awareness of historical misuses of science (De Block and Adriaens, 2013). There is detailed advice on the handling of dual use research of concern provided by the Joint Committee (“Joint Committee on the Handling of Security-Relevant Research”) of the German National Academy of Science Leopoldina and the German Research Foundation (DFG) (2022). The Joint Committee also provides networking and exchange opportunities for Committees for Ethics in Security-Relevant Research (Kommissionen für Ethik sicherheitsrelevanter Forschung), so-called KEFs. Nevertheless, additional information and guidance on handling dual use research of concern is a regular request in particular from scientists, but also a request often heard in forums with policy experts, managers and administrators of institutions in research and education. The present guideline provides such additional in-depth information on the definition, examples, legal as well as ethical issues and options for governance of dual use research. It has been written by ethicists and philosophers of technology, supported by lawyers and members of the commission for ethics in research of Forschungszentrum Jülich. It is intended to provide additional information supporting the design of and deliberation in institutional bodies dealing with ethics of security-relevant research. It aims to highlight decisions and options relevant to different institutions and refers to further sources of information throughout.

Purpose This systematic review aims to identify factors that influence parents’ decisions regarding pediatric diagnostic and predictive genetic testing (DT/PT). Factors are integrated into a conceptual model of decision-making. Implications for genetic counseling, research, and ethics are derived. Methods PubMed, PsychInfo, WebofScience and references of related reviews were searched for original publications between 2000 and 2023. Extracted factors were categorized into an existing model. Results Of 5843 publications, 56 met inclusion criteria. The included studies differentiate between DT, traditional, and expanded PT and describe factors impacting parental decisions on both to have the child genetically tested and to be informed about additional findings. Factors included: 1. benefits/hopes, 2. worries/concerns, 3. values and beliefs, 4. individual circumstances, and 5. emotional states. Conclusion Our work extends an existing empirical decision model of family decisions about genome sequencing to genetic testing in pediatrics in general, adding the categories “individual circumstances” and “emotional states”. The factors can be further integrated into the Health Belief Model; the importance of emotional states is reflected in dual-process theories, such as Fuzzy Trace Theory. Research is required on emotional states, differences between DT and PT, parents’ decisions about result disclosure, and dyadic variables as decision-making predictors.

Simple Summary Are we morally justified in using animals in biomedical research and if so, how can we make sure that the experiments are conducted in a scientifically and morally acceptable manner? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor. Thus, our article aims to contribute to the foundation of the emerging field of animal research ethics, combining perspectives from research ethics, animal ethics, science, and law. In doing so, we describe the following seven phases that animal experiments typically run through: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI). Here, 20 key ethical, legal, and practical challenges are identified and analyzed that need to be addressed. Apart from challenges arising at the level of the experiments themselves, there are also so-called meta-challenges associated with animal research ethics as a field. Four of these are presented and further discussed, also in relation to their opportunities for the further development of animal research ethics that takes into account interdisciplinary and international perspectives. Abstract Can nonhuman animals be used for the benefit of humans in a scientifically and morally justified manner and, if yes, how? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor, considering insights from research ethics and animal ethics as well as scientific and legal aspects. The aim of this article is to contribute to the foundation of the emerging field of animal research ethics. In doing so, we describe the following seven phases of animal research experiments: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI). In total, 20 key ethical, legal, and practical challenges that an ethical framework for the use of animals in research needs to address are identified and analyzed. Finally, we characterize the following four meta-challenges and opportunities associated with animal research ethics as a field: (1) moral pluralism, (2) the integration of views and positions outside the laboratory, (3) international plurality of conduct, standards, and legal norms, and (4) interdisciplinary education.

Driven by technological innovations, newborn screening (NBS) panels have been expanded and the development of genomic NBS pilot programs is rapidly progressing. Decisions on disease selection for NBS are still based on the Wilson and Jungner (WJ) criteria published in 1968. Despite this uniform reference, interpretation of the WJ criteria and actual disease selection for NBS programs are highly variable. A systematic literature search [PubMED search “Wilson” AND “Jungner”; last search 16.07.22] was performed to evaluate the applicability of the WJ criteria for current and future NBS programs and the need for adaptation. By at least two reviewers, 105 publications (systematic literature search, N = 77; manual search, N = 28) were screened for relevant content and, finally, 38 publications were evaluated. Limited by the study design of qualitative text analysis, no statistical evaluation was performed, but a structured collection of reported aspects of criticism and proposed improvements was instead collated. This revealed a set of general limitations of the WJ criteria, such as imprecise terminology, lack of measurability and objectivity, missing pediatric focus, and absent guidance on program management. Furthermore, it unraveled specific aspects of criticism on clinical, diagnostic, therapeutic, and economical aspects. A major obstacle was found to be the incompletely understood natural history and phenotypic diversity of rare diseases prior to NBS implementation, resulting in uncertainty about case definition, risk stratification, and indications for treatment. This gap could be closed through the systematic collection and evaluation of real-world evidence on the quality, safety, and (cost-)effectiveness of NBS, as well as the long-term benefits experienced by screened individuals. An integrated NBS public health program that is designed to continuously learn would fulfil these requirements, and a multi-dimensional framework for future NBS programs integrating medical, ethical, legal, and societal perspectives is overdue.

Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III).

This chapter examines whether high prices for gene therapies are justified and whether the problems associated with high prices can be solved by the "pay for performance" (P4P) reimbursement model. To this end, we first describe how prices for new drugs, including gene therapies, are set in Germany (section 2.). P4P is then presented as an example of a reimbursement model (section 3.). The subsequent ethical analysis (section 4.) first examines whether P4P models can sustainably guarantee the right to health and healthcare for all people (section 4.1; cf. on the "sustainable right to health" already Alex, 2021). It is then shown that cost-benefit analyses for setting prices for new gene therapies must be viewed critically from an ethical perspective and pose a problem for equity of access and thus also for the sustainable guarantee of a right to health (section 4.2). The final question is whether P4P is compatible with the idea of human dignity (Article 1 I 1 of the German Basic Law) (section 4.3; cf. already König et al., 2020). Alex, K. (2021): Ethical conceptualization of a sustainable right to health(care). In: Schildmann, J. et al. (eds.): Defining the value of medical interventions. Normative and empirical challenges. Kohlhammer, Stuttgart: 29-48. PMID: 36256802 König, J. et al. (2020): Am individuellen Therapieergebnis orientierte Erstattungsverfahren in der Onkologie: ethische Implikationen am Beispiel der CAR-T-Zelltherapie. In: Ethik Med 32: 85–92. doi: 10.1007/s00481-020-00565-3.

Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers’ health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers’ minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality. This article presents a comprehensive literature review, and analysis by interdisciplinary experts of the scientific, legal, ethical, and societal issues surrounding epigenetics and the military. Notwithstanding the potential benefit from these applications, our findings indicate that the current lack of scientific validation for epigenetic technologies suggests a careful scientific review and the establishment of a robust governance framework before consideration for use in the military. In this article, we highlight general concerns about the application of epigenetic technologies in the military context, especially discrimination and data privacy issues if soldiers are used as research subjects. We also highlight the potential of epigenetic clocks to support child soldiers’ rights and ethical questions about using epigenetic engineering for soldiers’ enhancement and conclude with considerations for an ethical framework for epigenetic applications in the military, defense, and security contexts.

Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III).

Excerpt: 1. Introduction This chapter provides insight into the diverse ethical debates on genetics and epigenetics. Much controversy surrounds debates about intervening into the germline genome of human embryos, with catchwords such as genome editing, designer baby, and CRISPR/Cas. The idea that it is possible to design a child according to one’s personal preferences is, however, a quite distorted view of what is actually possible with new gene technologies and gene therapies. These are much more limited than the editing and design metaphors suggest. Such metaphors are therefore highly problematic phrases in the context of new gene technologies, for two reasons. On one hand, to design a child of choice by modifying the genome would require modifying any gene of choice, which is more than can be done with current gene technologies, such as CRISPR/Cas. On the other hand, a modification of genes would need to be enough to create any characteristic of choice in the future child. The latter presupposes the assumption of genetic determinism. Moreover, the CRISPR/Cas technology can not only be used in a potentially therapeutic manner at the germline level. In addition, there is the (more likely) scenario of a future clinical therapeutic use of these new gene technologies for modifying the DNA sequence of other cells of the body (somatic genome editing). There is also the option of modifying the epigenome, that is, the spatial configuration of DNA (epigenome editing) (see table 1). Like genetics and genome editing, epigenetics has been at the center of recent popular scientific and ethical discourse as well as scientific debates. The concept of epigenetics has given rise to very different notions of inheritability and responsibility for health, which, however, are oftentimes based on scientifically controversial basic assumptions. That there continues to be covert genetic determinism in the form of epigenetic determinism (see table 2) in debates about epigenetics has been pointed out in ethical analyses of epigenetics. Neither genetic determinism nor epigenetic determinism has been confirmed scientifically. It is therefore important to recognize the concepts that are discussed (and sometimes harshly criticized) in debates about genome editing and epigenetics—for example, concepts about the causal role of DNA for our own life course. This importance is based on the fact that if we understand such controversial concepts, we will be able to remain critical when evaluating scientific knowledge and ethical arguments about genome editing and epigenetics. This chapter, therefore, explains some of these concepts. For an ethical analysis of epigenetics as well as of genome editing, it is necessary to understand and critically reflect upon the underlying concepts of genetic determinism and other, related -isms. The following section offers a detailed introduction to these -isms (section 2; see also table 2). Section 3 provides an ethical analysis of genome editing and epigenetics based on the explanations in section 2. Section 3 focuses on inheritability and responsibility, justice, safety, the problem of consent, and the effects of genome editing and epigenetics on embryos and future generations. This section does not discuss in detail further points that can be found in ethical debates about epigenetics as well as in ethical debates about genome editing. These points include (among others): • fear that the findings of epigenetics and that the methods of genome editing are misused—this also with respect to eugenics and enhancement; • naturalness—an issue we mention in passing a few times in the following analysis; • a possible connection between the genome/epigenome and the concept of human dignity, and the derived danger of instrumentalization and infringement of autonomy when intervening in the genome or epigenome. Since current discourse about ethical issues associated with genome editing focuses mainly on germline interventions, which are, for instance, interventions into a human embryo’s genome, we mainly focus on germline interventions when comparing the debates on genome editing and on epigenetics in section 3.

Despite a vast amount of discussions on sustainability and on the right to health(care) within applied ethics, it has not been precisely determined how both concepts can be connected. This article argues that a sustainable right to health(care) comprises an agent-relative right to health(care), an agent-neutral right to health(care), economic aspects, and (only included in the conceptualization of a sustainable right to health, not to healthcare) environmental aspects. It starts with a formal outline of the argument in the form of numbered premises, with reference to the sections of the paper where the respective premises are analysed (section 1). It then summarises the idea that a sustainable right to health, encompassing the right to healthcare, rests on the assumptions of normative realism, of agent-relative and agent-neutral values (Nagel, 1986), and on the traditional concept of sustainability (Elkington, 1999) (sections 2 and 3). Concomitantly, the International Covenant on Economic, Social and Cultural Rights’ (ICESCR, 1966) outline of the right to health and the World Commission on Environment and Development’s (WCED, 1987) definition of sustainability are evaluated. Finally, the proposed concept is discussed from the perspective of different countries and with a focus on the conflict between economic and ethical, as well as agent-relative and agent-neutral aspects of a sustainable right to health(care) (section 4). Repeatedly in sections 3 and 4, germline genome editing is taken as an example for the suggested approach, as the health of future generations is, on the one hand, reflected in the idea of a sustainable right to health(care) and, on the other hand, is essential when discussing the right to this novel technology.

Abstract: This working paper focuses on the question whether there is a therapeutic imperative that, in specific situations, would oblige us to perform genome editing at the germline level in the context of assisted reproduction. The answer to this central question is discussed primarily with reference to specific scenarios where preimplantation genetic diagnosis (PGD) does not represent an acceptable alternative to germline genome editing based on either medical, or ethical, or – from the perspective of the potential parents – moral or religious grounds. This article deals with four different types of case constellations that result from these possible reasons against PGD as well as from the necessity or dispensability of a subsequent “control PGD.” These cases are discussed based on hypotheses concerning contextual factors and theoretical assumptions. In conclusion, we point out that if our assumptions are correct, there is probably no therapeutic imperative for genome editing at the germline level. We draw this rationale from the fact that germline interventions are likely not person-affecting. However, we caution the reader that our result is preliminary and needs to be more carefully examined in future work in light of the bioethical debate and potential objections. // Abstract: Im Zentrum dieses Working Papers steht die Frage, ob es einen therapeutischen Imperativ geben kann, der uns, in bestimmten Situationen, verpflichten würde, eine Genomeditierung (genome editing) auf Keimbahnebene im Rahmen der assistierten Befruchtung vorzunehmen. Die Antwort auf diese zentrale Frage wird insbesondere mit Bezug auf Fälle diskutiert, in denen das Verfahren der Präimplantationsdiagnostik (PID) keine aus entweder medizinischen oder ethischen oder – aus Sicht der potentiellen Eltern – moralischen bzw. religiösen Gründen akzeptable Alternative zu einem Keimbahneingriff darstellt. Die möglichen Gründe gegen die PID sowie die Erforderlichkeit oder Verzichtbarkeit einer nachfolgenden «Kontroll-PID» ergeben vier verschiedene Fallkonstellationen, denen sich der Beitrag zuwendet. Auf Grundlage von Hypothesen zu kontextuellen Faktoren und theoretischen Annahmen diskutieren wir diese Fälle. Im Ergebnis verweisen wir darauf, dass es, wenn unsere Annahmen zutreffen, vermutlich keinen therapeutischen Imperativ zum genome editing auf Keimbahnebene gibt. Dies begründet sich daraus, dass der Keimbahneingriff vermutlich nicht als personenbezogen (person-affecting) zu bezeichnen ist. Wir weisen jedoch darauf hin, dass unser Ergebnis vorläufig ist und unter Berücksichtigung der bioethischen Debatte und möglicher Einwände genauer geprüft werden muss. // Résumé: Ce Working Paper se concentre sur la question de l’existence d’un impératif thérapeutique qui, dans des situations spécifiques, nous obligerait à réaliser une édition du génome au niveau de la lignée germinale dans le cadre de la procréation assistée. Afin de répondre à cette question centrale nous développons quatre scénarios spécifiques dans lesquels le diagnostic préimplantatoire (DPI) ne représente pas une alternative acceptable à l’édition du génome germinal pour des raisons médicales, éthiques ou – du point de vue des futurs parents – morales ou religieuses. Cet article traite de quatre constellations différentes de cas résultant des raisons mises en avant pour s'opposer au DPI ainsi que de la nécessité ou de l’inutilité d’un ultérieur « DPI de contrôle » Ces cas sont discutés sur la base d’hypothèses portant sur les facteurs contextuels et sur les présupposés théoriques. En conclusion, nous soulignons que si nos hypothèses sont correctes, il n’y a probablement aucun impératif thérapeutique justifiant l’édition du génome au niveau de la lignée germinale. Nous arrivons à cette conclusion parce qu’une intervention au niveau de la lignée germinale n’est probablement pas susceptible d’affecter la personne. Cependant, nous mettons en garde le lecteur sur le fait que notre conclusion est préliminaire et qu’elle doit être examinée avec soin dans des futurs travaux instruits par le débat bioéthique et par les éventuelles objections.

Dupras and Bunnik’s strong statement against the normative approach of genetic exceptionalism, which can no longer be justified in the midst of multi-omic research, is of great importance fofor sound ethical reasoning about omic data. Furthermore, the authors’ explicit critique of a sole focus on genomics in normative considerations about data security and especially their nuanced depiction of sensitivity, (re)identification risks and discriminatory potential associated with epigenomic data in research and in private, commercial so-called “direct- to-consumer” epigenetic testing (as specified in earlier works) might be a stepping stone for broadening the scope of normative discussions in other gene-ethics debates. Debates about therapeutic applications of tools such as CRISPR/Cas for example currently focus primarily on the genome and not on potential applications and ethical consequences of epigenome editing. Overcoming an exceptional focus on genomics and genetics by including the role of epigenomics into a primarily genome-centered normative debate is necessary to accommodate evolving biomedical fields of research. By means of conceptual clarification especially of the term “multi-omic contextualism” (Dupras and Bunnik 2021, 49) this commentary on Dupras, C., and E. M. Bunnik, "Toward a framework for assessing privacy risks in multi-omic research and databases" (The American Journal of Bioethics 2021 21 (12): 46–64. doi:10.1080/15265161.2020.1863516) argues that Dupras and Bunnik’s framework might currently be rather exceptional than contextual especially because extrinsic data properties are not primarily considered and that the framework is di-omic (genomic-epigenomic) rather than multi-omic because the meaning of multi-omics within the article appears to imply contextual factors. The highly relevant normative ideas on the problem of (re)identification risks and sensitivity of other than genomic, especially epigenomic, data presented by the authors are nevertheless, as Dupras and Bunnik assume (2021), likely to be relevant even beyond omics, for example, for imaging data, and it might thus be evaluated in future research whether multi-omic exceptionalism/contextualism could present a novel form of biological reductionism (Waggoner and Uller, "Epigenetic determinism in science and society," New Genetics and Society 2015 34 (2):177–95. doi: 10.1080/14636778.2015.10330522015), especially if primarily focused on the analysis of genomics and epigenomics. Dupras and Bunnik’s framework might then be made even stronger by making it broader.

Slightly modified excerpt from the section 13.4 Zusammenfassung und Ausblick (translated into english): This chapter is based on an analysis of ethical debates on epigenetics and genome editing, debates, in which ethical arguments relating to future generations and justice play a central role. The analysis aims to contextualize new developments in genetic engineering, such as genome and epigenome editing, ethically. At the beginning, the assumptions of "genetic determinism," on which "genetic essentialism" is based, of "epigenetic determinism" as well as "genetic" and "epigenetic exceptionalism" are analyzed and critically discussed. The remarks on the ethical discourse on epigenetics show that the notion of "epigenetic determinism" can sometimes be discerned not only in popular scientific discourse but also in ethical discourse. Ethical debates on epigenetics, however, have distanced themselves from this deterministic understanding. As a result, the focus in the ethical discourse on epigenetics shifts from responsibility for one's own health and that of subsequent generations to justice. What is meant here is justice, for example, in terms of access to healthy environmental conditions, regardless of whether these contribute to health with or without epigenetic agency. An analysis of the discourse on genome editing reveals that it is primarily germline interventions that are being ethically examined, with a concentration on the aspect of inheritance. The question is whether this is accompanied by an implicit "genetic determinism" or even a "genetic essentialism": the determinism could lie in the centrality of the aspect of heritability, since only genetic information is inherited. Does the aspect of heritability and genome modification play a more decisive role in debates on genome editing than the safety issue? Is the problem of embryos and their potential offspring not being able to consent to germline intervention given such a high priority because it is a genetic intervention? Under such a premise of "strong genetic determinism" supplemented by "epigenetic determinism," not only genome editing but also epigenome editing would be ethically relevant precisely because it too would have an influence on the genome. How this influence of genome editing and epigenome editing is ethically evaluated in each case therefore depends initially on whether the assumptions of "genetic" and "epigenetic determinism" are advocated. These assumptions are increasingly viewed critically in ethical discourse because they cannot be confirmed from a scientific perspective. In popular scientific debates in particular, however, they seem to persist, which ultimately also influences the public discussion. Since a broad public discussion is required especially on genome editing, a reflective approach to the various "-isms" analyzed in this chapter is central. DOI: 10.5771/9783748927242.