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. 2022 Dec 20;15(2):189–204. doi: 10.1007/s41649-022-00234-1

Mapping the ‘Ethical’ Controversy of Human Heritable Genome Editing: a Multidisciplinary Approach

Richard Pougnet 1,2, Benjamin Derbez 1,3, Marie-Bérengère Troadec 2,4,5,✉
PMCID: PMC10076464  PMID: 37035482

Abstract

Genome editing, for instance by CRISPR-Cas, is a major advancement of the last 10 years in medicine but questions ethically our practices. In particular, human embryo heritable genome editing is a source of great controversy. We explored how this ethical question was debated in the literature from PubMed database, in a period of 4 years (2016–2020) around the announcement of the ‘CRISPR babies’ Chinese experiment in November 2018. We evaluated the weight of the arguments for and against this topic, through an analysis of reviews published on this question. The most important arguments come from the technical perspective: safety issues and benefits, putative long-term effects on the future generations and the need to assess this aspect. Next, foreseeable clinical benefits and the alternatives to these methods are discussed. The number of people that would benefit from such techniques is also considered. However, social and anthropological issues are addressed in a more disparate way. Parenthood and desire for children are sometimes overlooked. Few authors mention social justice, stigmatisation and equality of access. Consent and information are more clearly addressed, as well as the question of the relationship between generations. Finally, the effects on the nature of humankind or human species are far from being consensual; the risks of enhancement, eugenics and transhumanism are raised. We conclude that the risks associated with the immaturity of the technique were at the forefront of the ethical debate on human embryo heritable genome editing. Their consequences were seen as more immediate and easier to handle than those of sociological or anthropological projections, which are more speculative in nature.

Supplementary Information

The online version contains supplementary material available at 10.1007/s41649-022-00234-1.

Keywords: Genome editing, Human heritable genome editing, Embryo, CRISPR

Introduction

Exploring how the problem of human embryo heritable genome editing (HHGE) has been considered and debated in the scientific literature is important when dealing with the 10th anniversary of the ‘genome editing by CRISPR-Cas9 technique’. To do so, we question how the controversy of HHGE was handled when the international scientific community was not fully prepared for it, when guidelines were not clearly proposed. Indeed, at the end of 2019, the Chinese researcher He Jiankui was found guilty by the Chinese justice to have ‘unlawfully carried out the genetic manipulation of embryos for reproductive purposes’ and was condemned to 3 years in prison. This verdict has gained a broad consensus in the international biomedical science community and beyond. Are ethical common grounds shared at the international level to reach this consensus? Which are they? Can we say that this agreement among experts indicates the existence of a common sense of ethics at the international level? Is this apparent agreement a sign of universal values or ethical standards, which He Jiankui flagrantly violated by his work in 2018?

The question of the universality of ethical standards and values has been discussed in the field of bioethics for many years (Beauchamp and Childress 1979; Engelhardt 1996). Pluralism of conceptions of good in multicultural societies and transnational spaces is a well-established fact that challenges moral rationality in its pursuit of absolutes. The social sciences have shown the relativity of certain bioethical values, such as autonomy, presented as fundamental, universal and anhistorical (Kleinman 1997; Wolpe 1998; Fox and Swazey 2008, i). Nevertheless, this de facto relativity has never implied a relativism of rights, nor does it invalidate the pursuit of universal ethics, from a common sense of morals that allows the international community to react when faced with behaviours harmful to humanity (Kleinman 1999). From this point of view, HHGE applied to embryos constitutes an interesting case study to freshly re-examine the values and standards by which these practices were condemned. In what way are these values and standards ethical? Is there a specificity of the ethics in the domain of values and standards or are we moving towards a minimalist ethic (Ogien 2021)? Above all, we need to consider the nature of the arguments brought into this controversy and determine to what extent the experiments performed by He Jiankui incited ethical arguments.

To address these questions, we analysed the main reviews published on HHGE applied to reproduction from October 2016 until November 2020. This cut-off corresponds to a period of 2 years before and after the first report in 2018 of the experiments performed by He Jiankui. The intense controversy within the scientific community that developed during those years interested us, because it took place between two moments of the regulation of the uses of CRISPR-Cas9: one before the condemned experiment applied to human reproduction (Baltimore et al. 2015, 2018; National Academies of Sciences, Engineering, and Medicine 2017; Yeung et al. 2018) and the other after its condemnation. Apart from the normative analysis of the evolution of the guidelines before and after He Jiankui’s experiment, it is interesting to focus on the description of the ethical debate itself as it unfolded over this period. Categorising the arguments used in the debate led us to reveal the supremacy of technical considerations, in particular the safety issues, into this ethical debate, and to support the idea of a great porosity between the technical, scientific, socio-political and anthropological fields in the reviews on this subject.

Methodology

Many review articles have been published regarding ‘CRISPR babies’ or embryo HHGE, each with a specific focus depending on the stage of development of scientific and medical knowledge, as well as scientific and public controversies. These review articles, which summarise the state of knowledge in this topic, constitute a rich material that gives a synthetic view of the state of the controversy at different times and from different points of view. In our work, we propose a critical and reflective reading of those review articles. Drawing on the ‘controversy mapping method’ (Latour 2007; Venturini et al. 2015), we built a classified overview of the different arguments identified in the review articles. This method does not necessarily imply reference to primary sources (original articles, opinion pieces, editorials, etc.) insofar as the objective is to give an overview of the controversy during a given period. Therefore, we have chosen to select only review articles. This work allowed us to discuss the nature and relative importance the different ethical arguments in the controversy raised by HHGE. Our analysis was based on articles gathered according to the following search method: on 16 November 2020, we made a PubMed search based on the criteria ‘genome editing human embryo ethics’ under the filter: ‘review’. The date of November 2020 was chosen because it was within the immediate first 2 years after the communication of He Jiankui’s experiment on embryo HHGE by CRISPR-Cas, and importantly before publication of renewed international guidelines taking the ‘He Jiankui affair’ into account (for instance guidelines from International Society for Stem Cell Research (ISSCR)). We considered this period because review articles on HHGE by CRISPR-Cas mirrored, then, immediate reactions and thoughts. This search retrieved 26 articles among which eight were excluded because six were off-topic and two were not in English or French. Thus, in total, 18 articles were included in our analysis (Fig. 1, Online resource 1). Each article was read by two independent readers and screened for the different types of arguments (Fig. 2). For each argument, we took in consideration whether it was present or not in the review articles (qualitative assessment), and how much it is discussed compared to the other arguments (quantitative assessment).

Fig. 1.

Fig. 1

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Diagram representing the selection of the articles

Fig. 2.

Fig. 2

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Scheme of the methodology of analysis of the classification of the arguments

Results

We have classified the arguments that are mobilised on HHGE. We have organised the different types of arguments into two parts: one on the CRISPR-Cas technique, its limits and potentials (part 1), the other on the human and social sciences (part 2) (Fig. 3A and B).

Fig. 3.

Fig. 3

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A multidisciplinary mapping of the main arguments brought into human embryo genome editing controversy and their relative weight. A Qualitative assessment of the presence of each argument (% of articles with a given argument). B Quantitative assessment of the argument (relative representation of an argument in a given article)

The Arguments based on the Technique are Extensively Developed to Explore the Safety Issue and its Benefits

The Criterion of Safety is First Addressed from the Technical Point of View

Most of the reviews we analysed on embryo HHGE start with the presentation of the technique used (Fig. 3A and B). Although, from a technical point of view, what is generally first highlighted is a greater accuracy of CRISPR-generated genome editing compared with prior methods of gene editing and its efficiency (Harper and Schatten 2019), three main technical limitations are consistently reported:

  1. Off-target effects. Off-target effects designate physiological changes caused by unintended modifications in genetic loci that were not specifically targeted by the CRISPR design (Vassena et al. 2016; Jouannet 2017; Musunuru 2017; Plaza Reyes and Lanner 2017; Harper and Schatten 2019; Niemiec and Howard 2020; Lei and Qiu 2020). It is of note that the frequency of these off-target modifications is still poorly described in embryos.

  2. Mosaicism. The targeted edited changes may be generated in only some cells of early-stage embryos, leaving some cells unedited. Two issues may arise from mosaicism: the first is the unpredictability of the physiological outcome of the genome editing (Vassena et al. 2016; Lei and Qiu 2020) and the second is the possible perpetuation of the disease (transmission to the next generation of unedited cells) (Lei and Qiu 2020).

  3. Uncontrolled on-target effects. Intended mutagenesis may not be effective on the targeted sites (Musunuru 2017) or unintended mutation may be generated on-target (Niemiec and Howard 2020).

These three technical limitations (off-target effects, mosaicism and unintended on-target effects) are systematically categorised as safety issues. The discussion that subsequently arises from these review articles often aims to determine to what extent these safety issues may be a limit or an opportunity for HHGE. Indeed, some authors judge these safety issues unacceptable, while others consider them a challenge. In other words, some authors consider that the CRISPR technique, despite its promise, is not safe and not mature enough for application to human embryos (Vassena et al. 2016; Plaza Reyes and Lanner 2017; Jouannet 2017; Lei and Qiu 2020; Meagher et al. 2020) while other authors propose to determine what level of uncertainty for this technique we are able or willing to accept, and to address the question of the evidence that would be needed to proceed to first-in-human use (Davies et al. 2019; Niemiec and Howard 2020). Altogether, the consensus argument on safety is well summarised by Meagher et al. (2020): ‘The science shows promise but needs further safety testing’.

The Criterion of Safety Is Then Addressed from the Long-Term Perspective, as Is the Subsequent Issue of Assessing This Aspect

Long-term benefits or potential harmful effects that may arise in the prospective children and also their descendants are not known (Ishii 2017a, b). Therefore, clinical trials should include, a minima, the long-term follow-up of subjects (Cwik 2020). Moreover, over a longer time scale, long-term benefits of such a decrease in prevalence of genetic diseases should be considered not just at the level of an individual and their descendants, but at a population level (Niemiec and Howard 2020). However, the complex relationship between genes and their environment, where a certain variant of a gene can be an advantage at present and deleterious in the future, may render this assessment unrealistic (Camporesi and Cavaliere 2016).

The Question of the Clinical Foreseeable Benefits is Necessarily Discussed

In general, the utility (benefit) of the CRISPR technique used on human embryos is proposed at three levels: first, to increase knowledge, then to reduce consequences of genetic diseases and, third, for enhancement. Obviously, not all three levels correspond to direct medical benefits.

The clinical utility of HHGE is, in one way or another, discussed by more than 80% of the articles (Fig. 3A), and corresponds approximately to 20% of each article (Fig. 3B). The straightforward way to present the clinical benefits of embryo HHGE is ‘to fight disease and reduce suffering’ hereby justifying a moral imperative to develop these techniques (Munsie and Gyngell 2018; Adashi and Cohen 2018).

More specifically, the main clinical applications that are proposed consist in the:

  1. Treatment of genetic disease or infectious disease (Lei and Qiu 2020). Some authors argue that germline/embryo genome editing is an option for not transmitting a defective gene (Niemiec and Howard 2020). However, few authors appropriately highlight that this manipulation applied to human embryos is not about treatment since it is used to create a child with a specific trait rather than to treat an already existing child (Niemiec and Howard 2020).

  2. Treatment of infertility. HHGE may increase reproductive autonomy (Vassena et al. 2016).

  3. Prevention in offspring and future generations of genetic diseases and other gene-related diseases, including infectious diseases, cancers, cardiovascular diseases, drug dependency, obesity, and so on, which may otherwise be inherited from the family (Lei and Qiu 2020), and improve resistance to disease (Niemiec and Howard 2020). This latter argument is highly questionable; the goal may not be achieved as it proposes to prevent multigenic and multifactorial diseases (Vassena et al. 2016).

An important point is to evaluate whether these uses are therapeutic or for non-medical applications, since the former would legitimate their use whereas the latter would disqualify them (Cwik 2020). Enhancement is clearly controversial (Harper and Schatten 2019).

Last, but not least, the goal of having healthy and genetically related children (Lei and Qiu 2020; Niemiec and Howard 2020), or even the desire to design a child according to parents’ preferences (Lei and Qiu 2020) is a subject well worth discussing (see part 2 anthropology and sociology).

Alternatives are Discussed in 60% of the Articles, from those that Avoid Manipulating the Genome to those Proposing to Use of Other CRISPR-Cas

Most authors considered that embryo HHGE should only be considered when reasonable, already established methods, not entailing embryo genome manipulation, are unavailable (Vassena et al. 2016; Munsie and Gyngell 2018). Proposed alternatives range from those that do not manipulate the genome to those that manipulate the non-embryo genome.

Among the possible reasonable alternatives, three mean accepting to have a non-genetically related child. For the couples, these consist in (1) adopting a child, (2) deciding to not have a child together or (3) using donor gametes (Niemiec and Howard 2020).

When a couple decides to still attempt to have a genetically related child, many established reasonable methods already exist that do not involve genome manipulation. Among these (1) alternative treatment or prevention can be followed. In the specific example of HIV infection, other safe and effective methods to prevent HIV infection exist (Meagher et al. 2020). Those alternatives do not involve embryo nor gamete manipulations. (2) Many authors recognise that, in the majority of cases, in vitro fertilisation (IVF) coupled with preimplantation genetic diagnosis can be applied to achieve similar purposes to CRISPR editing in order to have a genetically related child not affected by a disease. Therefore, embryo HHGE does not seem to have a clear advantage over it (Vassena et al. 2016). In fact, the only case where genome embryo editing might potentially be the only alternative to have a genetically related child not affected by a disease would be when both (i) the targeted disease is monogenic and (ii) when both parents are homozygous for a recessive mutation or one parent is homozygous for a dominant disease. Such cases are rare.

When genome manipulations are still envisioned in order to have a genetically related child, again, alternative methods exist that do not modify the embryo genome. They consist of (1) somatic editing. Most of the clinical applications of CRISPR will not lie in editing the germline, but in editing somatic tissues (Camporesi and Cavaliere 2016); (2) genome manipulation of gametes or germinal cells just before fertilisation (Vassena et al. 2016); (3) editing of induced pluripotent stem cells (IPS) prior to intracytoplasmic sperm injection (ICSI) (Vassena et al. 2016).

Finally, when embryo genome manipulation is foreseen, the use of the variant of CRISPR/Cas9 genome editing that performs base editing rather than DNA cutting would be safer, although the possibility of off-target base edits still needs to be carefully examined (Greenfield 2018).

The Argument of the Number of People That Would Benefit from Those Techniques Is Still Considered

The question of the number of people that would benefit from genome editing and its consequences is brought into the discussion in 25% of the articles (Vassena et al. 2016; Niemiec and Howard 2020; Lei and Qiu 2020) (Fig. 3A). Despite the fact that it is not always clearly stated, the underlying idea is about maximisation of benefits to the majority/largest number of people. Some authors, therefore, consider using HHGE for prevention purposes as a ‘moral imperative’ because it will benefit billions of people around the world over time (Savulescu et al. 2015). However, other authors perform different calculation and consider that the number of people that would really use CRISPR germline HHGE for therapeutic purposes are few (Vassena et al. 2016; Niemiec and Howard 2020). For instance, it is estimated that in the USA in a given time there is only one couple of reproductive age in which both partners are homozygous for gene variants causing cystic fibrosis (Niemiec and Howard 2020).

In the end, whether the number of couples who could potentially make use of CRISPR HHGE for therapeutic reasons is considered high or low, this question of ‘numbers’ is often asked, showing that its answer is a relevant argument for or against HHGE. A bias in the ethical reasoning process can be noted here. It does not appear to us to be universally accepted that maximising the benefits for the greatest number of people is always a guarantee of morality.

Altogether, in each review article we analysed on HHGE, this part on technical issues and benefits is the most developed section. The authors scrupulously screen for technical arguments to address, consciously or not, the different criteria from the Declaration of Helsinki: ‘All medical research involving human subjects must be preceded by careful assessment of predictable risks and burdens to the individuals and groups involved in the research in comparison with foreseeable benefits to them and to other individuals or groups affected by the condition under investigation’ (World Medical Association 2013). Next, the authors enter into additional arguments of interest to the field of social and human sciences. We will explore these in the following sections.

Sociological and Anthropological Questions are Addressed in a More Disparate and Heterogeneous Manner

Parenthood and the Desire for Children Are Crucial Issues in This Debate but Are Sometimes Overlooked

From a social point of view, some authors emphasise that HHGE represents a way to help couples ‘prevented’ from having children by the risks of serious genetic diseases for their offspring (Camporesi and Cavaliere 2016; Lea and Niakan 2019; Lei and Qiu 2020). In this regard, the technique would make it possible to correct a natural injustice and re-establish equality between couples with regard to the wish to have children. However, this progress in the access to parenthood is tempered in many papers by the author’s emphasis on the social risks associated with this technology. Among these, the risk of the ‘commodification of babies’ has been underlined (Adashi and Cohen 2018). Similarly, the temptation for couples to ‘design’ their child is also mentioned (Lei and Qiu 2020; Niemiec and Howard 2020). The risk of destabilising the family (between the ‘modified’ children and the others, the parent–child relationship) has also been brought up (Ormond et al. 2017). Just beyond these questions is another that deserves attention, that of knowing, more broadly, whether the use of embryo HHGE would increase social expectations of technologies likely to embody the idea of the ‘right to a child’ (Camporesi and Cavaliere 2016).

Social Justice, Stigma and Equal Access should be Strong Arguments in this Debate, but Few Authors Ultimately Build their Conclusions on them

Finally, some authors point out that facilitating access to biological parenthood for parents at risk of transmitting of genetic diseases could undermine adoption systems by reducing the pool of couples likely to adopt children, who would then be left behind in the wake of technological progress (Ishii 2017a, b). In line with this argument, Niemiec and Howard add that the control of individuals’ genomic characteristics could increase intolerance of difference and make the place of people born with disabilities even less secure in our societies (Niemiec and Howard 2020). People with genetic abnormalities would then be considered as unjustified burdens on society (Lei and Qiu 2020). Handicap is defined as a mismatch between the environment and an individual’s abilities. If fewer people were disabled, there could be a decrease in the overall amount of support required. On the contrary, some authors report the real possibility of societal stigma of the first generation of edited subjects (Cwik 2020). This stigmatisation would be caused by infrequency and novelty, but above all to a birth resulting from an illicit situation, sometimes considered immoral. Therefore, applying a technique to counter social injustice could lead to more discrimination and social injustice. Some authors also question the equality of access to these techniques (Vassena et al. 2016; Adashi and Cohen 2018). Ishii, for example, asks whether the cost of these technologies will mean that only the wealthiest will be able to use them (Ishii 2017a, b).

The Issue of Consent and Information is Clearly Addressed in Half of the Articles and, Furthermore, Raises Questions about Intergenerational Relationships

Genetic modification of humans to come implies examining the question of the relationship between generations. What about consent when parents decide to modify the genome of a future child? When parents decide to allow embryonic genome modification, the CRISPR baby would not be able to retrospectively refuse the modification; some authors condemn the impossibility for the child to exercise their autonomy in such circumstances (Cwik 2020).

Another question concerns how a CRISPR baby would be informed of their origin. Would the parents tell their children and, if so, how would they do this? It is realistic to expect that the parents would be ashamed or proud about the means of reproduction and this might lead them to lie to their children (Meagher et al. 2020)? Additionally, a CRISPR baby could question its own reproductive life, in part because HHGE could induce adverse effects on future generations. They will also face the question of stigmatisation but, this time, between two generations: the constitutively genetically modified one and the somatically or not genetically modified one. Indeed, Lei and Qiu report ‘If so, the population of the persons with genetic condition would be divided into two groups: one group of the persons with genetic condition would be cured by somatic cell genome editing, and their children would be born with the genetic condition prevented.’ (Lei and Qiu 2020). Furthermore, the difficulty of assessing long-term adverse effects raises questions about the responsibility of the present generation towards future generations. Consequently, Lei and Qiu state ‘So our responsibility for the future generations is not limited (to) the impact of global warming, and the deteriorating of environment caused by our current way of life, but also to the way of human reproduction including heritable genome editing applied to human reproduction.’ (Lei and Qiu 2020).

Arguments Questioning the Effects on Human Nature and Species are Far from Unanimous; the Risks of Enhancement, Eugenics and Transhumanism are More Often Raised

Our analysis of the literature brings to light a certain number of arguments that could be considered anthropological.

Genome editing at the embryonic level has a direct impact on the constitutional genome of the individual. For some, the status of the morula, then the embryo and foetus, may be viewed differently from that of a human being after birth, making the use of the CRISPR technique on embryos ethically justified (Lei and Qiu 2020). For others, on the contrary, a human being is a full human person from the embryonic stage. In this case, it is the dignity or value of human life that is put into question by the genomic editing of embryos (Vassena et al. 2016).

Furthermore, Lei and Qiu also discuss and refute Habermas’ argument of respecting the ‘Nature of Man’ (Lei and Qiu 2020). For Lei and Qiu ‘If the purpose of genetic engineering (e.g. heritable genome editing) is only for preventing the decedents from thalassemia, what it would affect on their human nature? It would not prevent them from becoming themselves, and instead, it may make one become oneself much better.’ This type of argument rightly fuels the fears of those who are concerned about respect for the disabled, as in the case of Niemiec, who writes: ‘An increased focus on avoiding certain traits and increasing others may also lead to a decrease of compassion and general acceptance of disabled persons in society.’ (Niemiec and Howard 2020). Here the question of eugenics is also massively raised, implicitly for some and explicitly for others (Vassena et al. 2016; Niemiec and Howard 2020).

Beyond the question of future generations, it is also the future of the human species that is at stake (Munsie and Gyngell 2018). The use of CRISPR-Cas would give humans the power to directly influence the evolution of their own species (Adashi and Cohen 2018). This practice, as a logical extension of the idea of the Anthropocene, is interpreted by some authors as symptomatic of humanity ‘playing God’ by developing artificial beings, which goes against human nature (Lei and Qiu 2020). As a counter-argument, some authors propose an application limited to therapeutic uses, producing effects on the species similar to techniques already in use. Vassena writes ‘Still, as long as the techniques are used to correct defects and diseases, their effects would be similar to preimplantation and prenatal screening applied at the moment.’ (Vassena et al. 2016).

From this stems a reflection on the purpose of these modifications. The possibility they could be used for enhancement is then pointed out (Lei and Qiu 2020; Niemiec and Howard 2020). Although this use is controversial (Harper and Schatten 2019), some dispute the argument of the slippery slope that would necessarily lead, step by step, from genome editing to enhancement or even transhumanism (Fogleman et al. 2016).

Discussion

At the end of this meta-analysis of review articles about HHGE around the birth of the first CRISPR babies in China in 2018, it is possible to draw two conclusions and to formulate several questions.

In terms of findings, our reading of the main review articles selected shows the greater weight of scientific and technical arguments compared with social and anthropological ones (Fig. 3B). The dangers posed by HHGE due to the immaturity of the technique are at the forefront of the controversy. Their consequences are seen as more immediate than those of sociological or anthropological projections, which are more speculative in nature.

This conclusion seemed to be confirmed, at that time, by an expert international report published in 2020 that pointed out that ‘the technology is not presently ready for clinical application’ (Ledford 2020) and which recommended a moratorium on its use. Without going into the details of the ethical debates, the author goes over the steps that scientists would have to validate before generating genetically modified babies if the States were to grant them the right to do so in the future (2020). However, the WHO considered the main regulation issues to be ethical and social (Baylis 2019).

The second conclusion that can be drawn concerns the main type of approach taken to ethics in the articles. Whether it is an evaluation of the safety of the technique or reflections on its socio-anthropological issues, the argumentation perspective is situated in the field of consequentialist ethics. Most of the arguments outlined are concerned with the analysis of the possible or probable consequences, positive or negative, of the use of the genome editing technique at the level of the embryo. The ‘moral luck’ argument, for example, according to which it will be through the prism of the subsequent reception by society that a transgression will be judged as reprehensible (bad) or a stroke of genius (good), is indeed part of this consequentialist perspective, although the object of evaluation is more the opinion generated by the act and not the result of the act itself, in terms of health, overall good or pleasure. It is, therefore, striking to see the absence of deontological arguments in the debates. We can propose several hypotheses to explain this situation.

The first hypothesis concerns the methodology of our approach. One can ask whether there was selection bias in the way we constituted our corpus of articles. We worked with PubMed, a bibliographic search engine for biomedical journals. Although this search engine references the main biomedical journals including the bioethics ones, it is possible that the proximity of these journals to the field of medical and life sciences research enhances the focus on a pragmatic approach to ethics characteristic of consequentialism. This raises the question of whether other ethical approaches (deontological or virtue-based) might not have been taken in other publications not listed in the content aggregator we used. A further exploratory search made using the same keywords, but on the JSTOR database, did not yield any significant results for the same period of time (articles up to November 2020). However, a more in-depth bibliographical study could allow us to make a more precise test for this bias.

The second hypothesis that can be made concerns the very nature of ethics as an autonomous field of reflection. An analysis of the articles shows that ethical reflections are constantly integrated into the reasoning of different scientific or technical fields. For example, many articles warn readers about fairness of access to genome editing techniques. The authors assume that the techniques are expensive, which would make access to the new reproduction unequal between people of different income levels. This question, therefore, raises political issues of the universality of health systems in different countries. Hence, the impression of porosity between the fields of ethics and politics arises from bioethical debates. The controversy surrounding the embryo HHGE shows that the major bioethical principles (justice, autonomy, beneficence, etc.) cannot be thought of or implemented without taking into account the scientific, social and political contexts of which they are part. This is linked to the very development of bioethics as a multidisciplinary area of reflection, addressing the societal issues of biotechnologies (Jonsen 1993). This second hypothesis consists in asserting that in the field of biomedicine, ethics is necessarily a ‘mixed or combined’ discipline, a reflection on norms and values embodied in technologies, knowledge, devices, institutions and historical and social anthropological realities. Putting into perspective the ethical reasons for deciding whether a particular act is good can only be done with knowledge of the act and its ins and outs. The bioethics that developed in the twentieth century is no longer the reflection of post-war theologians and philosophers; it is a transdisciplinary field that requires an understanding of a subject in all its dimensions, whether clinical, political or social. Since Beauchamp and Childress transposed the principles of the Belmont Report to clinical practice (Beauchamp and Childress 1979), the principles of bioethics have largely infiltrated medical practice. However, other principles could also have informed the reflection on the case of CRISPR babies. For example, the European Biomed II project highlights four important concepts in bioethics and biology in Europe: autonomy, dignity, integrity and vulnerability (BIOMED II Project 1998). From this point of view, and knowing that the first case of CRISPR babies in 2018 was perhaps more a matter of clinical practice than of research, the principles of integrity and vulnerability could have been discussed for these children. Above all, it would have been possible, and probably more consensual, to talk about the vulnerability of the couple whose members were asymmetrically HIV-positive and healthy, in terms of health asymmetry.

Conclusion

Genome editing is a major advancement in medicine and genetics in particular of the last 10 years, and as such, questions, scientifically and ethically, our practices. Based on the analysis of review articles concerning the debates about the HHGE of embryos, we have been able to examine how this bioethical debate was handled immediately after the report of He Jiankui’s experiment. The categorisation of the different arguments mobilised for or against the development of this technology has enabled us to reveal the importance of technical considerations. Those considerations on safety seemed to be shared by the entire scientific community. We also show the great porosity that exists between techno-scientific arguments on the one hand, and socio-anthropological arguments on the other, in the ethical debate. This observation tends to support the idea that ethics is embodied in the discourses and practices of all the actors concerned by a biomedical technology such as CRISPR-Cas. Not all scientists or technicians are moral philosophers but are, in practice, ethicists in their activities. Ethics is embodied in the choices made at all levels, whether scientific, technical, social or political. This implies that the bioethical debate should be truly interdisciplinary. Finally, our analysis argues for ethical questioning in anticipation of dilemmas. The temporal dimension of the ethical questioning has clearly appeared, which had led to a moratoria from many actors at that time, waiting for international guidelines. Since experimental development provides the means to an end, it is this end that must be questioned from the outset. This work on the controversy on HHGE of embryos may be informative for the next challenges that medicine will face in the next 10 years.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 132 KB) (132.3KB, docx)

Abbreviations

CRISPR

Clustered Regularly Interspaced Short Palindromic Repeats

WHO

World Health Organisation

Author Contribution

RP, BD and MBT have analysed the data and written the manuscript.

Funding

The authors thank the Département des Sciences Humaines et Sociales, UFR de Médecine et Sciences de la Santé, Université de Bretagne Occidentale, for its financial support.

Data Availability

Not applicable.

Declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. Adashi EY, Cohen IG. Preventing mitochondrial diseases: Embryo-sparing donor-independent options. Trends in Molecular Medicine. 2018;24:449–457. doi: 10.1016/j.molmed.2018.03.002. [DOI] [PubMed] [Google Scholar]
  2. Baltimore, David, Françoise Baylis, Paul Berg, George Q. Daley, Jennifer A. Doudna, Eric S. Lander, et al. 2015. On Human Gene Editing: International Summit Statement. National Academies of Sciences, Engineering, and Medicine, 3 December 2015. https://www.nationalacademies.org/news/2015/12/on-human-gene-editing-international-summit-statement. Accessed 12 Dec 2022.
  3. Baltimore, David, Alta Charo, George Q. Daley, Jennifer A. Doudna, Kazuto Kato, Jin-Soo Kim, et al. 2018. Statement by the Organizing Committee of the Second International Summit on Human Genome Editing. National Academies of Sciences, Engineering, and Medicine, 8 November 2018. https://www.nationalacademies.org/news/2018/11/statement-by-the-organizing-committee-of-the-second-international-summit-on-human-genome-editing. Accessed 12 Dec 2022.
  4. Baylis, Françoise. 2019. Un an après les premiers bébés CRISPR, des normes plus strictes sont en place pour éviter les dérives. The Conversation, 19 December 2019. https://theconversation.com/un-an-apres-les-premiers-bebes-crispr-des-normes-plus-strictes-sont-en-place-pour-eviter-les-derives-128767. Accessed 12 Dec 2022.
  5. Beauchamp TL, Childress JF. Principles of biomedical ethics. New York: Oxford University Press; 1979. [Google Scholar]
  6. Camporesi S, Cavaliere G. Emerging ethical perspectives in the clustered regularly interspaced short palindromic repeats genome-editing debate. Personalised Medicine. 2016;13:575–586. doi: 10.2217/pme-2016-0047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cwik Bryan. Responsible translational pathways for germline gene editing? Current Stem Cell Reports. 2020;6:126–133. doi: 10.1007/s40778-020-00179-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davies, Kay E., Richard P. Lifton, Hidenori Akutsu, Robert Califf, Dana Carroll, Susan Golombok, et al. 2019. International commission on the clinical use of human germline genome editing - call for evidence. National Academies of Sciences, Engineering, and Medicine.
  9. Engelhardt TH. The foundations of bioethics. New York: Oxford University Press; 1996. [Google Scholar]
  10. Fogleman S, Santana C, Bishop C, Miller A, Capco DG. CRISPR/Cas9 and mitochondrial gene replacement therapy: Promising techniques and ethical considerations. American Journal of Stem Cells. 2016;5:39–52. [PMC free article] [PubMed] [Google Scholar]
  11. Fox RC, Swazey JP. Observing bioethics. New York: Oxford University Press; 2008. [Google Scholar]
  12. Greenfield A. Carry on editing. British Medical Bulletin. 2018;127:23–31. doi: 10.1093/bmb/ldy020. [DOI] [PubMed] [Google Scholar]
  13. Harper JC, Schatten G. Are we ready for genome editing in human embryos for clinical purposes? European Journal of Medical Genetics. 2019;62:103682. doi: 10.1016/j.ejmg.2019.103682. [DOI] [PubMed] [Google Scholar]
  14. Ishii, Tetsuya. 2017a. Germ line genome editing in clinics: The approaches, objectives and global society. Briefings in Functional Genomics 16(1): 46–56. 10.1093/bfgp/elv053. [DOI] [PMC free article] [PubMed]
  15. Ishii, Tetsuya. 2017b. The ethics of creating genetically modified children using genome editing. Current Opinion in Endocrinology, Diabetes and Obesity 24(6): 418–423. 10.1097/MED.0000000000000369 [DOI] [PubMed]
  16. Jonsen AR. The birth of bioethics. Hastings Center Report. 1993;23:S1–4. doi: 10.2307/3562928. [DOI] [PubMed] [Google Scholar]
  17. Jouannet P. CRISPR-Cas9, germinal cells and human embryo. Biologie Aujourd'hui. 2017;211:207–213. doi: 10.1051/jbio/2017032. [DOI] [PubMed] [Google Scholar]
  18. Kleinman A. Moral experience and ethical reflection: Can ethnography reconcile them? A quandary for “the new bioethics”. Daedalus. 1999;128:69–97. [PubMed] [Google Scholar]
  19. Kleinman A. Writing at the margin: discourse between anthropology and medicine. Berkeley: University of California Press; 1997. [Google Scholar]
  20. Latour, B. 2007. La cartographie des controverses. Technology Review 0: 82–83.
  21. Lea R, Niakan K. Human germline genome editing. Nature Cell Biology. 2019;21:1479–1489. doi: 10.1038/s41556-019-0424-0. [DOI] [PubMed] [Google Scholar]
  22. Ledford H. ‘CRISPR babies’ are still too risky, says influential panel. Nature. 2020 doi: 10.1038/d41586-020-02538-4. [DOI] [PubMed] [Google Scholar]
  23. Lei R, Qiu R. Ethical and regulatory issues in human gene editing: Chinese perspective. Biotechnology and Applied Biochemistry. 2020;67:880–891. doi: 10.1002/bab.2032. [DOI] [PubMed] [Google Scholar]
  24. Meagher KM, Allyse MA, Master Z, Sharp RR. Reexamining the ethics of human germline editing in the wake of scandal. Mayo Clinic Proceedings. 2020;95:330–338. doi: 10.1016/j.mayocp.2019.11.018. [DOI] [PubMed] [Google Scholar]
  25. Munsie M, Gyngell C. Ethical issues in genetic modification and why application matters. Current Opinion in Genetics and Development. 2018;52:7–12. doi: 10.1016/j.gde.2018.05.002. [DOI] [PubMed] [Google Scholar]
  26. Musunuru, K. 2017. The hope and hype of CRISPR-Cas9 genome editing: A review. JAMA Cardiology 2: 914–919. 10.1001/jamacardio.2017.1713. [DOI] [PubMed]
  27. National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. 10.17226/24623 [PubMed]
  28. Niemiec E, Howard HC. Ethical issues related to research on genome editing in human embryos. Computational and Structural Biotechnology Journal. 2020;18:887–896. doi: 10.1016/j.csbj.2020.03.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ogien R. La panique morale. Paris: Grasset; 2021. [Google Scholar]
  30. Ormond KE, Mortlock DP, Scholes DT, Bombard Y, Brody LC, Faucett WA, Garrison NA, Hercher L, Isasi R, Middleton A, et al. Human germline genome editing. American Journal of Human Genetics. 2017;101:167–176. doi: 10.1016/j.ajhg.2017.06.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Plaza Reyes A, Lanner F. Towards a CRISPR view of early human development: Applications, limitations and ethical concerns of genome editing in human embryos. Development Cambridge England. 2017;144:3–7. doi: 10.1242/dev.139683. [DOI] [PubMed] [Google Scholar]
  32. Savulescu J, Pugh J, Douglas T, Gyngell C. The moral imperative to continue gene editing research on human embryos. Protein and Cell. 2015;6:476–479. doi: 10.1007/s13238-015-0184-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vassena R, Heindryckx B, Peco R, Pennings G, Raya A, Sermon K, Veiga A. Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Human Reproduction Update. 2016;22:411–419. doi: 10.1093/humupd/dmw005. [DOI] [PubMed] [Google Scholar]
  34. Venturini T, Ricci D, Mauri M, Kimbell L, Meunier A. Designing controversies and their publics. Design Issues. 2015;31:74–87. doi: 10.1162/DESI_a_00340. [DOI] [Google Scholar]
  35. Wolpe PS. The triumph of autonomy in American medical ethics: a sociological view. In: DeVries R, Subedi J, editors. Bioethics and society: sociological investigations of the enterprise of bioethics. New York: Prentice Hall; 1998. [Google Scholar]
  36. World Medical Association. 2013. WMA Declaration of Helsinki – ethical principles for medical research involving human subjects. [DOI] [PubMed]
  37. Yeung, Karen, Richard Ashcroft, Neva Haites, Joyce Harper, Julian Hitchcock, Jackie Leach Scully, Tony Perry, and Christine Watson. 2018. Genome editing and human reproduction: social and ethical issues. Nuffield Council on Bioethics, 17 July 2018. http://nuffieldbioethics.org/project/genome-editing-human-reproduction.

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