The frequency of endorsements, rejections and mentions of a reason cannot, on its own, lead us to a conclusion about that reason’s cogency, or about the merits of the arguments in which that reason is deployed. Nonetheless, our categorization and documentation of reasons concerning chimera research yields a descriptive account of the current debate, allowing us to highlight noteworthy trends, argumentative clusters and interesting patterns within the discussion.
Positive reasons (category P)
(15% of all coded passages. Distribution within: 31% mentions, 7% rejections, 61% endorsements)
It is striking that discussions of positive reasons (Category P) constitute a rather small fraction of all passages retrieved (15%). Additionally, these positive reasons are mostly endorsed (61%) or mentioned (31%), and only rarely rejected (7%). Both phenomena can be accounted for.
The relatively low frequency of passages referring to positive reasons might be explained by the fact that engaging with these reasons often involves speculation concerning whether certain states of affairs will obtain. In particular, endorsing or rejecting these reasons mainly depends on scientific or medical prognosis (will chimera creation lead to advances in basic research or will it not (P.1), will chimera research foster the development of application options or will it not (P.2)?). Additionally, it is largely uncontroversial that these potential advances in basic and applied research are morally desirable and they thus do not form an attractive basis for an in-depth ethical discussion. By contrast, more intricate ethical questions concerning competition and allocation of resources are framed negatively and are thus grouped under downstream effects (D.2.ii). Authors of papers retrieved in a survey of ethical arguments are likely to focus on ethically controversial issues that call for discussion and analysis, while, at the same time, they may not be ideally placed to predict in a detailed manner just what benefits we might expect to obtain from chimera research. It is therefore unsurprising that these authors do not engage primarily with positive reasons, focusing instead on the more ethically controversial issues in the negative categories.
Concerning the relatively low rejection rate of positive reasons, suggestions that chimeras might contribute to basic research or could lead to valuable applications are rather vague, making targeted criticism difficult. Rejections in this field would mainly have to amount to accusations of “overselling”. This skepticism, however, is not easy to substantiate. Furthermore, it would require detailed predictions of benefits, which, as noted above, are not likely to form a central focus in the ethical literature.
Negative reasons (categories A-D)
(85% of all coded passages. Distribution within: 46% mentions, 34% rejections, 20% endorsements)
The four remaining negative categories focus on more ethically controversial issues, require more ethical analysis, and involve, on the whole, less detailed empirical conjecture. This is particularly the case for the categories concerning chimera treatment (B) and chimera existence (C). For example, suggestions that bringing a chimera into existence might violate human-analogous respect (B.2.i) or that the existence of chimeras might threaten human dignity (C.1.i) requires discussion of ethical concepts (just what do human-analogous respect and human dignity amount to, and why would chimera research threaten these standards?). In addition, these discussions do not necessarily have to assume that a very specific type of chimera will exist, as, for example, any chimera with human-associated capacities or with a sufficient amount of human material might invoke concerns of human respect and human dignity (even if the existence of these types of chimeras remains, for the moment, rather visionary). To be sure, some of these issues do involve a certain degree of empirical conjecture (relatively specific capacities will be relevant to some reasons in the chimera treatment category (B), such as the contention that certain types of chimeras would seriously suffer (B.1.i), or that ill-treatment will result from the chimera having a human-like consciousness (B.2.ix)). Similarly, other arguments rely on certain psychological or sociological postulates (for example, reasons in the chimera existence category (C) assume that there are certain social taboos that the existence of chimeras might violate (C.1.iii), or that important psychological and social barriers will be threatened by the existence of chimeras, leading to moral confusion (C.2.i)). Even in these cases, however, there are hotly debated ethical concepts and issues that require sustained discussion to make a case that we should (or should not) view this as a serious ethical problem (could this suffering be justified in certain circumstances, why should a human-like consciousness be avoided, is there anything wrong with violating taboos, why is moral confusion a problem?).
It should also be noted that some of the ethical issues raised by chimera research are familiar from other bioethical contexts. This is particularly true for reasons concerning chimera creation (A), chimera treatment (B – particularly B.1, where the chimera is presumed to have animal-analogous moral status) and downstream effects (D), which refer to common problems of animal experimentation (A.1, B.1), the use of human biological material (A.2), safety (D.1, D.2.i), and justice (D.2.ii). It is thus unsurprising that, in a survey of academic literature, which is inherently striving for originality and innovation, these reasons are reiterated relatively infrequently (B.1, D), or merely mentioned rather than discussed in a sustained manner (A). In addition, the safety-based concerns in D.1 and D.2.i, like the positive reasons, are predicated on specific scenarios coming to pass (will it indeed be the case that the results of chimera research pose a threat to the individual (D.1) or to biosafety in general (D.2.i), and, if so, how significant are the risks?). Although there is a more controversial ethical issue at the heart of these concerns than within the category of positive reasons (which risks would be acceptable?), this question is not an attractive candidate for sustained ethical consideration, due to the fact that it is not specific to chimera research and thus tends to bypass the discussion of novel issues in favor of appeals to general moral standards concerning risk-taking.
Finally, the fact that more articles are concerned with negative reasons (A-D) than with positive reasons (P) does not imply a negative attitude towards chimera research, as reasons discussed might only be mentioned, or even ultimately rejected rather than endorsed by the author. At the same time, however, the fact that reasons in the negative categories (A-D) exhibit an overall surplus of rejections (34%) over endorsements (20%) does not indicate a positive attitude towards chimera research either, as it is possible to repudiate certain reasons against conducting chimera research without approving of the practice overall.
Reasons concerning chimera creation (category a)
(11% of all coded passages. Distribution within: 58% mentions, 28% rejections, 13% endorsements)
The relatively infrequent appearance of passages within this category (11%) might be attributed to the fact that these reasons rehash well-known arguments concerning the treatment of animals in research (A.1) and the use of human biological material, including human embryos and human eggs (A.2) (see above). As such, arguments dealing with these issues can be found in existing bioethical literature, requiring only minor amendments for application to the cases at hand. There is thus a limited incentive for authors to engage in sustained discussion of reasons pertaining to chimera creation. Of course, this by no means precludes their practical relevance.
Reasons concerning chimera treatment (category B)
(23% of all coded passages. Distribution within: 33% mentions, 27% rejections, 40% endorsements)
The chimera treatment category is composed of two broad reason types – one based on the assumption that chimeras will have animal-analogous moral status (B.1), while the other proceeds from the assumption that chimeras will have human-analogous moral status (B.2). The relatively high proportion of endorsements (40%) compared to rejections (27%) for both broad reason types might be a result of the fact that challenging these reasons is likely to be based on specific assumptions about the capacities of chimeras (for example, doubting that chimeras would ever attain human-analogous capacities (see B.2.ix)), which, as noted above, may not be the area of expertise of many authors writing ethical papers. It is only in very few cases that it seems possible to challenge these arguments through questioning the moral standards to which they appeal (for example, by arguing that a being with a certain potential is not necessarily owed corresponding developmental options (see B.2.iii)), but generally, the moral standards invoked are largely uncontroversial. Thus, while pointing out problems with chimera treatment may involve novel ethical discussion (through highlighting novel dangers of maltreatment, instrumentalization etc. in biomedical practice), the repudiation of these arguments will mostly be a matter of suggesting that these potential scenarios will not ultimately materialize.
Reasons predicated on the idea that chimeras have animal-analogous status (B.1) suffer from the familiarity of animal ethics arguments in general, which could explain their infrequent representation in comparison to reasons which involve speculation that a chimera might have human-analogous moral status (B.2). As above, this does not preclude their importance in practice, particularly as the notion of a chimera with human-analogous traits is rather speculative. Furthermore, it should be noted that concerns with animal protection are distributed between the chimera treatment category (B, specifically B.1) and the chimera creation category (A, specifically A.1), depending on whether the authors are concerned with harms to animals in the chimera generation process, or to the resulting animal-analogous chimera. Animal issues thus make up a greater proportion of the debate than may be apparent at first glance.
Reasons concerning chimera existence (category C)
(46% of all coded passages. Distribution within: 49% mentions, 39% rejections, 12% endorsements)
Reasons concerning chimera existence make up a significant proportion of all retrieved passages (46%). One explanation for this, and particularly for the higher prevalence of discussions concerning chimera existence (C) compared to discussions concerning chimera treatment (B), is that much discussion of the latter involves scrutiny of specific types of chimeras (the origin of a chimera’s cells, or its prospective capacities, etc., are likely to be relevant factors in determining how it should be treated). Reasons concerning chimera existence, by contrast, mostly deal with human-animal chimeras in general, invoking the potential metaphysical or social implications of these beings’ mere presence.
The overall proportion of rejections (39%) in the chimera existence category is quite high compared to endorsements (12%). The particularly low frequency of endorsements of reasons C.1.iii-C.1.vi (stating that the creation of chimeras might violate moral taboos, meet with instinctive repugnance, corrupt the natural order, or amount to playing God), relative to mentions and rejections, may suggest that discussions and refutations of these reasons are, predominantly, targeted at straw men. Alternatively, these reasons could appear, or be perceived to appear, in lay discourse, rather than in scholarly debate.
The fact that reason C.2.i (chimeras might generate moral confusion) has so few endorsements and so many mentions and rejections may be an editorial artefact. The first paper to advance this reason was a target article in the American Journal of Bioethics [73] and thus was accompanied by a series of open peer commentaries, which tend to take a critical stance toward the article they address.Footnote 3
Reasons concerning downstream effects (category D)
(5% of all coded passages. Distribution within: 52% mentions, 29% rejections, 19% endorsements)
Reasons concerning downstream effects constitute the least debated category (5%). Due to the paucity of data, reliable trends cannot be identified. There are several possible explanations for the infrequent discussion of downstream effects within the debate. First, the calculation of downstream effects requires making concrete predictions about the results of chimera research (whether, for example, they are likely to present threats to safety). This is compounded by the fact that the concerns discussed in this category often require far-reaching forecasts of consequences in the distant future, which are even more difficult to predict. The relatively far-off nature of these potential consequences also means that they might be viewed as less immediately urgent. Finally, the safety (D.1, D.2.i) and justice-based (D.2.ii) concerns contained in downstream effects are not specific to chimera research, but could be invoked in any biomedical context. All of these aspects might contribute to downstream effects being less attractive candidates for discussion.
Limitations
Although we devised the conception and methodology of our work with close regard to its purpose and demands, this study has certain limitations that need to be critically addressed. More precisely, these limitations concern the risks of: (1) data not being comprehensively included in our survey; (2) results not being unanimously extractable from the data; (3) conclusions not being readily inferable from the results.
Limitations of data, due to selection criteria and search procedures
As noted above (see Methods), we restricted our review of academic literature to English sources and to articles in international peer-reviewed journals. The restriction to English literature risks overlooking arguments from other cultural spheres. However, because English has become the dominant language for international bioethical discourse, we are confident that our data accurately reflects the scholarly debate at an international level. The restriction to peer-reviewed journal articles might also lead to the inadvertent exclusion of certain arguments. However, the inclusion of non-peer-reviewed literature would make it difficult to consistently exclude lay sources, feature pages, and other public opinion position papers. In addition, reports, surveys, encyclopedia entries, handbook articles etc. often summarize existing debates, and thus may lead to a distortion of data through a double-counting of reasons. The restriction to English [95,96,97,98] and peer-reviewed journal articles [95,96,97, 99, 100] is common in systematic reviews of reasons.
Additionally, it is possible that not all publications conforming to our selection criteria were included, because they do not appear in the databases searched, or because our search strings did not pick them up. It is also possible that, of the articles retrieved, we failed to identify some articles that met our inclusion criteria. We attempted to mitigate the latter limitation by requiring consensus concerning inclusion.
Limitations of results, concerning the attribution of text passages to reason types
Because coding of the passages could not be based on a simple search for keywords or catch phrases (the word “dignity”, for example, is deployed both to express concerns about the treatment of a chimera and the integrity of the human species), reasons were identified by a close reading and analysis of the texts. This introduces the danger of subjectivity, which we attempted to mitigate by coding passages independently, and eliminating disparities through discussion.
Limitations of conclusions
As outlined above (see Discussion), the number of mentions, rejections and endorsements of specific reasons does not allow us to draw any normative conclusions about the quality of the arguments, but rather provides a purely descriptive account of the current debate. Even descriptive conclusions, however, can only be drawn with caution. As outlined in the discussion above, the frequencies of reason mentions, endorsements and rejections might often be explained as a function of the peculiarities of academic bioethical debate. In particular, it is thus possible that our results do not mirror the concerns that bioethicists (even the authors included in our review) would identify as the most pressing. For instance, a bioethicist might publish a paper on a novel issue due to its interesting implications, or to capitalize in a gap on the debate. At the same time, however, she might hold that the most urgent moral problems with chimera research are the more familiar bioethical problems (such as animal suffering or translational risk).