'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.
