19 April 2019

Gene Editing Reasons

'The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature' by Nienke de Graeff , Karin R. Jongsma , Josephine Johnston , Sarah Hartley and Annelien L. Bredenoord in (2019) 374(1772) Philosophical Transactions of the Royal Society B comments
 In recent years, new genome editing technologies have emerged that can edit the genome of non-human animals with progressively increasing efficiency. Despite ongoing academic debate about the ethical implications of these technologies, no comprehensive overview of this debate exists. To address this gap in the literature, we conducted a systematic review of the reasons reported in the academic literature for and against the development and use of genome editing technologies in animals. Most included articles were written by academics from the biomedical or animal sciences. The reported reasons related to seven themes: human health, efficiency, risks and uncertainty, animal welfare, animal dignity, environmental considerations and public acceptability. Our findings illuminate several key considerations about the academic debate, including a low disciplinary diversity in the contributing academics, a scarcity of systematic comparisons of potential consequences of using these technologies, an underrepresentation of animal interests, and a disjunction between the public and academic debate on this topic. As such, this article can be considered a call for a broad range of academics to get increasingly involved in the discussion about genome editing, to incorporate animal interests and systematic comparisons, and to further discuss the aims and methods of public involvement.
The authors comment
In the last two decades, a host of genome editing technologies has emerged that can edit the genome with progressively increasing efficiency and ease of use. These technologies are based on the use of sequencespecific engineered nucleases, such as Zinc Finger Nucleases, meganucleases, and Transcription Activator-Like Effector Nucleases (TALENs). In more recent years, genome editing was revolutionized by the emergence of Clustered Regularly Interspaced Palindromic Repeat (CRISPR) and the CRISPR-associated protein Cas9 (CRISPR associated protein 9). In parallel, new applications of these genome editing technologies have emerged, such as gene drives, which allow the rapid and dominant spread of gene alterations within a population or even a species. 
Overall, this new generation of genome editing technologies allows scientists to modify the genomes of non-human animals (from here on: ‘animals’) more precisely than classical transgenesis with comparably fewer off-target effects. Furthermore, engineered nucleases can introduce genetic changes without the use of foreign DNA. These genome editing technologies have a broad range of possible applications in animals, including to increase livestock productivity and disease resistance, create new animal models to study human disease, protect native species by eradicating invasive species, decrease or even eliminate vector-borne diseases such as malaria, and perhaps even resurrect extinct species. Comprehensibly, these technologies and their applications have sparked both excitement and apprehension, raising new questions on ethics and governance and generating significant debate in both academic and public spaces. 
Despite this ongoing debate, to our knowledge no comprehensive overview of the arguments raised in the academic discourse on genome editing in animals exists. Such an overview is a valuable contribution to the academic literature, as it provides insights into patterns of argumentation in the expert debate and can help uncover arguments that go unmentioned or are insufficiently conceptualized. It is particularly salient to study the academic debate since academic experts can have a strong influence on related policy and governance decisions. Moreover, insight into the academic debate is important for understanding whether it differs from the public debate and arguments. For technologies that have high societal impact, such as genome editing, it is important to bridge potential gaps between the public and academic discourse in the early phases of development. 
In this article, we present such a comprehensive overview by reporting the reasons for and against the development and use of genome editing technologies in animals as these have been mentioned in the academic literature. Subsequently, we critically assess the academic debate and identify perspectives, issues and arguments that are underrepresented in the existing literature.
After an identification of specific reasons they comment
To the best of our knowledge, this review constitutes the first systematic review of reasons for and against development and use of new-generation genome editing technologies in non-human animals as reported in the academic literature. Our review shows that a wide and diverse range of reasons is brought forward and provides a descriptive overview of these reasons, offering a starting point for subsequent further research and normative analysis. 
Importantly, many reasons mentioned in this review are not reasons for or against all uses of genome editing in animals. Instead, they point to possible conditions for responsible use of these technologies. For example, the fact that genetically modified mosquitoes could potentially have negative consequences by spreading the modified gene beyond the target population, could lead to the requirement that a first trial site be geographically isolated, such as an island . Our review also underlines that different ethical considerations may apply to different applications of genome editing in animals. From this point of view, the question to ask is not whether genome editing in general is ethically acceptable but under which conditions it could be. 
In what follows, we make four additional observations about the academic debate, and suggest areas for future research and analysis. In particular, we note a lack of disciplinary diversity in the authors shaping the academic debate, an underrepresentation of animal interests, a scarcity of systematic comparisons of potential consequences of using these technologies, and a disjunction between the public and academic debate on this topic. We will elaborate on these observations below. 
Critical appraisal of the academic literature 
Our findings provide insight into who is shaping the academic debate on the use of gene editing technologies in non-human animals. As Table 1 illustrates, while authors of different backgrounds are involved in this debate, the large majority are (mostly biomedical or veterinary) scientists, investigating the technical feasibility of different applications of genome editing in animals. Authors working in ethics, philosophy, and the social sciences are underrepresented. This lack of disciplinary diversity is particularly problematic as the debate moves from discussions of technical feasibility to (potential) real-world applications, in which academic experts will likely influence policy and regulatory decisions. To critically assess the applications of genome-editing in animals from different perspectives, a multidisciplinary and proactive evaluation of the technologies and their ethical and societal implications – for example through ethics parallel research – is essential. 
Our findings also illuminate characteristics of the specific reasons addressed in the literature. Given that this review concerns genome editing in animals, it is remarkable how few animal-related reasons have been put forward; most reasons for or against the use of genome editing in animals rest on human-related grounds. So far, little of the biomedical literature considers the welfare of (research) animals; for example, articles that mention off-target effects seldom consider whether these effects could have an impact on animal welfare. Similarly, both biomedical and ethical literature provide little reflection on species-specific considerations. Although the moral status and interests of non-human primates were raised, the moral status of other animals was rarely mentioned. Given that accounts of moral status are generally founded in sentience  and consciousness, the interests of other animals appear worthy of more attention within this debate. And while the relationship between humans and animals was brought up in several reasons, particularly those related to animal dignity, this relationship was never framed in terms of human virtues. Such an analysis might ask, for example, who we become when we use and alter animals in certain ways. Indeed, when it comes to ethical theory, we note that the most frequently reported reasons – to a large extent originating from biomedical literature – were consequentialist in nature, i.e. focusing on potential (positive or negative) outcomes of using genome editing technology in animals on human health, animal welfare or ecosystems. While an initial emphasis on consequentialism is consistent with general argumentative patterns around new and emerging science and technologies, other ethical theories are relevant to this debate and will also be necessary to understand and engage with public attitudes and concerns. 
Our third major observation is that surprisingly few articles engaged in a systematic comparison of the harms and benefits of the proposed application of genome editing compared to alternatives. This gap in the literature is noteworthy, as such systematic comparisons are necessary to draw conclusions about what would result in the best overall consequences. Such an analysis could draw on the principles of proportionality and subsidiarity. According to the principle of proportionality, potential benefits should be balanced against potential harms or risks; those that argue in favour or against (applications of) genome editing in animals ought to present an explicit comprehensive overview of the benefits, harms and risks in question and argue why the harms outweigh the benefits or vice versa. The principle of subsidiarity entails that a policy should only be used if there is no less harmful policy that would achieve the same result. This principle suggests that applications of genome editing ought to be compared to alternative policies in terms of potential harms and benefits, including the – often forgotten – benefits and harms of the status quo. In the case of gene drives, for example, potential ecological damage resulting from their use is a pressing concern, warranting a thorough inventory of related risks and harms. When weighing those risks and benefits, the principle of subsidiarity forces us – amongst other things – to balance the possible ecological damage of using gene drives to eradicate vector-borne diseases with the deaths that are now caused by these diseases and the ecological damage of using pesticides. This kind of analysis is consistent with calls from the scientific community to integrate comparative assessment of risks and benefits into the regulatory framework. Yet where some scientific reports define benefits in narrow economic terms, the principle of subsidiarity requires a broad definition of and metric for benefits that extend beyond economics. 
Finally, we observed a disjunction between the expert and public debate on this topic. Academic experts have made significant calls for public engagement with and debate about genome editing, particularly with regards to the possible use of gene drives. A study commissioned by the United Kingdom’s Royal Society explores public perceptions and the reasoning behind them. In both this study and the academic debate more generally, considerable weight is given to the potential for genetically modified animals to improve human health or (negatively) impact ecosystems. However, other public concerns regarding genome editing technologies are thus far underrepresented in or wholly absent from the academic literature, including the public concern for equity of access to genome editing technologies, questions about the just distribution of governmental funding of genome editing compared with other investments, and concerns about the commercialization of genome editing technologies. With regards to commercialization, members of the public have raised the worry that businesses could prioritize profit-making over the public good and could fail to provide a balanced representation of the benefits and risks of these technologies. The fact that these concerns are largely absent from the academic debate on genome editing in animals is particularly problematic given ongoing calls for public engagement, and raises interesting questions that relate to a broader discussion about what the rationale, form, and aim of public engagement should be. If the goals of such engagement are not merely to inform the public, but also to address societal challenges and to allow the public to be involved in shaping technological developments together with other stakeholders, then issues regarding commercialisation, distributive justice, and access to genome editing technologies should also be studied in the academic literature.