The concept of vulnerability has become widely acknowledged as a fundamental concept for medical ethics and research ethics, yet rarely considered with respect to ethical assessments of human germline genome editing. A first aim of this paper is to make vulnerability ethics considerations fruitful for issues related to these technical innovations. The possibility of altering the genome promises to overcome forms of vulnerability inherently connected to our existence as physical beings and would hence allow to increase the resilience of human (...) nature or even to move evolution forward by equipping people with new character traits and enhanced capabilities. I suggest a more fine-grained distinction of various applications purposes than the dichotomy of therapeutic and enhancement. I support the rejection of most application purposes as ‘therapeutic’ and claim that framing them as ‘therapeutic’ in the context of the current discursive constellation runs the risk of accentuating existing vulnerabilities. With respect to intergenerational responsibilities, I reject the view that editing the germline necessarily leads to corrupt intergenerational relations based on which it must be categorically excluded. I conclude that it is nevertheless important to take a very close look at the challenges that arise, especially from a vulnerability perspective, before irreversible facts are created overhastily. (shrink)

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). (shrink)

Procreative obligations are often discussed by evaluating only the consequences of reproductive actions or omissions; less attention is paid to the moral role of intentions and attitudes. In this paper, I assess whether intentions and attitudes can contribute to defining our moral obligations with regard to assisted reproductive technologies already available, such as preimplantation genetic diagnosis (PGD), and those that may be available in future, such as reproductive genome editing and ectogenesis, in a way compatible with person‐affecting constraints. I propose (...) the parent–child relationship argument, which is based on the moral distinction between creating and parenting a child. Hence, I first argue that intentions and attitudes can play a role in defining our moral obligations in reproductive decisions involving PGD. Second, I maintain that if we accept this and recognize reproductive genome editing and ectogenesis as person‐affecting procedures, we should be committed to arguing that prospective parents may have moral reasons to prefer reproduction via such techniques than via sexual intercourse. In both cases, I observe an extension of our procreative responsibility beyond what is proposed by the consequentialist person‐affecting morality. (shrink)

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. (shrink)

La edición genética tiene muchas aplicaciones en casi todos los ámbitos de la sociedad, pero también puede tener consecuencias impredecibles. La edición del genoma de la línea germinal humana es el centro de una discusión mundial. Debido al creciente número de cuestionamientos científicos, éticos y políticos, muchos sin una respuesta concreta, el consenso de la comunidad científica manifiesta que sería inapropiado modificar genéticamente embriones humanos. Se considera necesario un debate serio y abierto para decidir si se debe suspender o fomentar (...) la investigación en este sentido. En el presente documento, se exponen algunos argumentos audaces a favor de la eliminación de los genes nocivos del genoma humano y los riesgos que supone el eugenismo liberal. (shrink)

Volume 20, Issue 8, August 2020, Page 38-40.

In der ethischen und rechtlichen Debatte um den möglichen Einsatz neuer Techniken zur Genomeditierung spielt der Begriff der genetischen Veränderung eine zentrale Rolle. Während im Bereich der grünen Gentechnik intensive Debatten um seine Bedeutung geführt werden, wird dieser Umstand im Kontext gentechnischer Interventionen am Menschen weitgehend ausgeblendet. Der Aufsatz expliziert drei mögliche Bedeutungen genetischer Veränderung, namentlich: ein prozessuales, ein diachrones sowie ein klassenbezogenes Verständnis. Anhand zweier Szenarien zukünftig erwartbarer Keimbahninterventionen wird anschließend exemplarisch gezeigt, welche Konsequenzen die Begriffe für die Kennzeichnung (...) humaner Embryonen als genetisch veränderte Entitäten haben und was dies jeweils für eine ethische und rechtliche Bewertung von Keimbahninterventionen bedeuten würde. Dabei ergeben sich jedoch für jeden der Begriffe logische, konzeptionelle sowie Anwendungsprobleme, die es problematisch erscheinen lassen, Maßnahmen der Genomeditierung überhaupt unter Verweis auf einen Begriff der genetischen Veränderung rechtlich oder ethisch zu bewerten. Soll dieser Bezugspunkt dennoch aufrechterhalten werden, ist unter pragmatischen Gesichtspunkten letztlich nur ein prozessuales Verständnis genetischer Veränderung plausibel. (shrink)

CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics. Once introduced into a genome, stealth genetic editing by a gene drive genetic element would occur each subsequent generation irrespective (...) of whether reproductive partners consent to it and irrespective of whether the genetic change confers any benefit. By overriding the ability to ‘opt in’ to genome editing, gene drives compromise the autonomy of carrier individuals and their reproductive partners to choose to use or avoid genome editing and impose additional burdens on those who hope to ‘opt out’ of further genome editing. High incidence of an initially rare gene drive in small human communities could occur within 200 years, with evolutionary fixation globally in a timeframe that is thousands of times sooner than achievable by non-drive germline editing. Following any introduction of heritable gene drives into human genomes, practices intended for surveillance or reversal also create fundamental ethical problems. Current policy guidelines do not comment explicitly on gene drives in humans. These considerations motivate an explicit moratorium as being warranted on gene drive development in heritable human genome editing. (shrink)

Recent scientific advances in the field of gene editing have led to a renewed discussion on the moral acceptability of human germline modifications. Gene editing methods can be used on human embryos and gametes in order to change DNA sequences that are associated with diseases. Modifying the human germline, however, is currently illegal in many countries but has been suggested as a ‘last resort’ option in some reports. In contrast, preimplantation genetic diagnosis is now a well-established practice within reproductive medicine. (...) Both methods can be used to prevent children from being born with severe genetic diseases. This paper focuses on four moral concerns raised in the debate about germline gene editing and applies them to the practice of PGD for comparison: Violation of human dignity, disrespect of the autonomy and the physical integrity of the future child, discrimination of people living with a disability and the fear of slippery slope towards immoral usage of the technology, e.g. designing children for specific third party interests. Our analysis did not reveal any fundamental differences with regard to the four concerns. We argue that with regard to the four arguments analyzed in this paper germline gene editing should be considered morally as acceptable as the selection of genomes on the basis of PGD. However, we also argue that any application of GGE in reproductive medicine should be put on hold until thorough and comprehensive laws have been implemented to prevent the abuse of GGE for non-medical enhancement. (shrink)

With recent reports that a Chinese scientist used CRISPR-Cas9 to heritably edit the genomes of human embryos (i.e., germline editing) brought to term, discussions regarding the ethics of the technology are urgently needed. Although certain applications of germline editing have been endorsed by both the National Academy of Sciences (US) and the Nuffield Council (UK), this paper explores the ethical concerns related even to such therapeutic uses of the technology. Additionally, this paper questions whether the technology could ever feasibly be (...) contained to the therapeutic realm. Consequently, this paper necessarily considers the ethical concerns related to enhancement uses of the technology even if only therapeutic applications are initially considered. In light of the concomitant risks, this paper assesses the technology’s countervailing benefits to conclude they do not prevail given that similar outcomes can largely be achieved with existing technologies. Consequently, this paper recommends an international ban on germline editing. (shrink)

Novel technological developments mean that gene editing – making deliberately targeted alterations in specific genes – is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development (...) of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human – rather than simply to undertake gene editing because it can be done. (shrink)

Slightly modified excerpt from the section 13.4 Zusammenfassung und Ausblick (translated into englisch): 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. (shrink)

Human evolution sits at several important thresholds. In organic evolution, interplay between exogenous environmental and genetic factors rendered new phenotypes at rates limited by genetic variation. The interplay took place on adaptive fitness landscapes determined by correspondence of genetic and environmental relationships. Human evolution involved important emergences that altered the adaptive landscape: language, writing, organized societies, science, and the internet. These endogenous factors ushered in transformative periods leading to more rapidly evolving emergences. I explore the impact of development of emerging (...) biotransformative technologies capable of being applied to effect self-genetic modification and artificial intelligence-augmented cognition on the evolutionary landscape of phenotypes important to cognitive plasticity. Interaction effects will yield unanticipated emergences resulting in hyperrealm adaptive landscapes with more rapid evolutionary processes that feed back upon more fundamental levels while vastly outpacing organic evolution. Emerging technologies exist that are likely to impact the evolution of cognitive plasticity in humans in ways and at rates that will lead to societal upheaval. I show that the theoretical contribution of organic evolution in future human evolution is expected to become comparatively insignificant relative to that made by endogenous environmental factors such as external cognition aids and manipulation of the human genome. The results support the conclusion of a strong recommendation of a moratorium on the adoption of any technology capable of completely altering the course of human evolution. (shrink)