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Question

In our view, the above versions of the precautionary principle are not vulnerable to the standard objections to positive precautionary principles. They are not unduly conservative, they differ meaningfully from standard cost‐benefit analyses and, if properly applied, they do not lead to paradoxical conclusions. This is not to say that these forms of the precautionary principle are above question. However, given their prima facie plausibility, at a minimum they warrant further analysis

In this section, we want to draw attention to a general difficulty associated with applying the precautionary principle in the context of GGE. It might seem that insofar as GGE carries plausible and significant risks to future generations, most plausible versions of the precautionary principle would weigh against pursuing GGE. This is not necessarily the case, as failing to pursue GGE may also carry plausible and significant risks to future generations.

As described at the beginning of the article, one possible application of GGE is to eradicate recessive mutations and disease‐predisposing alleles. This would significantly improve the health of future generations; correspondingly, failing to use GGE for these purposes might indirectly threaten the health of future generations. In addition, consider a more direct argument for GGE, based on an argument recently advanced by Russell Powell: that unless we engage in GGE the population's genetic health will gradually decline, leaving future generations increasingly reliant on conventional medical technology. This is because (Powell argues) advances in conventional medicine have largely freed humankind from the pressures of natural selection, thereby leaving the human gene pool vulnerable to the accumulation of deleterious mutations. The risks of failing to engage in GGE are twofold. Firstly, future generations may need to dedicate substantial resources to correct for their poor state of genetic health, thereby tying up resources that could have been used to promote human well‐being in other ways. Secondly, as future generations become increasingly dependent on medical technology to achieve current levels of well‐being, they will also become increasingly vulnerable to catastrophic harm should conventional medicines become less readily available – for example, during a hypothetical future period of economic and political collapse. On Powell's view, GGE presents a valuable means of maintaining current levels of genetic health and shielding future generations from potentially catastrophic threats to their well‐being.

If Powell's analysis is correct, pursuing and failing to pursue GGE carry the sort of risks that might trigger (most of) the above precautionary principles. Both courses of action carry an extremely bad worst‐case scenario; both threaten to render public health less secure; both might cause people to fall below a sufficient level of well‐being; and both plausibly violate negative obligations to future generations. Viewed this way, the precautionary principles discussed in this article do not provide any clear guidance on whether GGE should be carried out.

In saying this, we are not making the well‐worn point that the precautionary principle can often be deployed both for and against the same policy. Although some versions of the precautionary principle can be used this way, these versions of the principle are vulnerable to the incoherence objection described earlier in this article and should therefore be rejected. Our argument is that the risks of pursuing and failing to pursue GGE seem largely symmetrical, which makes it practically difficult to determine what course of action the precautionary principle would ultimately recommend. It is therefore an open question whether the precautionary principle would weigh against GGE or whether it might (contrary to most commentators' expectations) actually support GGE.

This is partly due to our limited understanding of the risks of GGE. As gene editing technologies are developed further it will become more possible to quantify the relevant risks, which may determine the appropriate way to deploy the precautionary principle. For example, the risks associated with off‐target mutations will become better understood as gene editing becomes more widely used in different cell types. The risks of on‐target mutations will become better understood as we understand more about genetics and genotype‐phenotype relation. The risks of accumulating germline mutations due to modern medicine could be better quantified using intergenerational studies to look at the rate at which mutations are actually accumulating and where in the genome they are accumulating. Therefore, although it is currently difficult to apply most versions of the precautionary principle to GGE, this is partly due to epistemic limitations that may be overcome in coming years.

Furthermore, the precautionary principle does offer relatively clear guidance on one point: prima facie, precautionary principles provide reasons to prefer some applications of GGE over others. Specifically, the precautionary principles described in this article provide a reason to favour GGE research focused on maintaining genetic health, enhancing the human species' long‐term viability or negating existential risks over research aimed at modifying cosmetic traits and perhaps also over research aimed at promoting health beyond some sufficiently high level of well‐being. The latter practices – but not the former – would expose future generations to unbalanced long‐term risks of harm in exchange for short‐term benefits.

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11. CONCLUSION
The precautionary principle aims to influence decision‐making in contexts where some human activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding GGE. It is therefore surprising that the precautionary principle has received relatively little attention in the bioethics literature on gene editing. Where the precautionary principle has been discussed, it is generally assumed with minimal analysis that this principle would weigh against human germline modification and perhaps even rule it out altogether.

We hope to have provided a more detailed sketch of the significance of different kinds of precautionary principle for GGE. We have argued that, while negative precautionary principles can be pragmatically useful in some contexts, they have little to contribute to the policy debate surrounding reproductive GGE. Positive precautionary principles are more closely relevant. Positive precautionary principles recommend placing especial weight on avoiding certain kinds of threats, such as threats we are cognitively primed to undervalue, threats that are poorly understood, threats to the achievement of a sufficient level of well‐being and threats to health security. While it is difficult to derive any straightforward policy recommendations from these positive versions of the precautionary principle, plausible versions of it would endorse GGE in at least some contexts – in particular, contexts where GGE could be used to correct otherwise catastrophic genetic mutations and/or to promote the long‐term robustness of human populations. Given that the precautionary principle is generally deployed against GGE, we think this is an important insight.

Much work remains to be done before the precautionary principle can yield concrete recommendations regarding GGE. We nonetheless hope to have made some headway in this article by showing that the precautionary principle should not be rejected outright, clarifying what role it might be able to play and drawing attention to some of the key questions that still need to be resolved.

Answer 1

We believe that the versions of the precautionary principle discussed above are not susceptible to the typical criticisms aimed at positive precautionary principles. They are not overly cautious, they offer significant differences from conventional cost-benefit analyses, and, if applied correctly, they do not lead to contradictory outcomes. However, this does not imply that these interpretations of the precautionary principle are beyond critique. Their initial credibility, at the very least, justifies further examination.

In this section, we aim to highlight a common challenge related to the application of the precautionary principle in the context of germline gene editing (GGE). While it might be assumed that GGE poses credible and significant risks to future generations, suggesting that most reasonable interpretations of the precautionary principle would discourage GGE, this is not necessarily true, as abstaining from GGE could also pose considerable risks to future generations.

As mentioned earlier, one potential benefit of GGE is the elimination of recessive mutations and disease-causing alleles, which could significantly enhance the health of future generations. Conversely, not implementing GGE may indirectly jeopardize their health. Furthermore, Russell Powell has recently posited that if we do not pursue GGE, the genetic health of the population may decline over time, increasing future generations’ reliance on conventional medical interventions. Powell argues that advancements in conventional medicine have alleviated some of the pressures of natural selection, making the human gene pool susceptible to the build-up of harmful mutations. Non-engagement in GGE presents dual risks: first, future generations might need to invest considerable resources to address their compromised genetic health, diverting funds from other avenues to enhance human welfare; second, as they grow increasingly dependent on medical technology for well-being, they may become exceptionally vulnerable to serious consequences if these medical resources become scarce, particularly in the event of a major economic or political crisis. From Powell's perspective, engaging in GGE is a valuable strategy for sustaining current genetic health levels and protecting future generations from severe threats to their well-being.

If Powell's arguments hold true, both pursuing and not pursuing GGE involve risks that could activate many of the aforementioned precautionary principles. Each option presents dire worst-case scenarios, undermines public health security, risks lowering overall well-being, and likely breaches negative obligations to future generations. In this sense, the precautionary principles discussed in this article do not provide clear direction on whether GGE should be pursued.

However, we are not reiterating the common perspective that the precautionary principle can be used both in favor of and against the same policy. While some interpretations can be utilized in this manner, they are susceptible to the incoherence objection discussed earlier in this article and should thus be dismissed. Our contention is that the risks associated with both pursuing and abstaining from GGE appear largely symmetrical, complicating the determination of what course of action the precautionary principle would advocate. Consequently, it remains uncertain whether the precautionary principle would oppose GGE or, contrary to most experts' assumptions, actually support it.

One reason for this uncertainty is our limited understanding of the risks associated with GGE. As gene-editing technologies advance, it may become easier to quantify the relevant risks, which could clarify how to appropriately apply the precautionary principle. For instance, the risks tied to unintended mutations will be better understood as gene editing is implemented across various cell types. Increased knowledge of genetics and genotype-phenotype relationships will illuminate the risks of such mutations. Additionally, intergenerational studies may help quantify the accumulation of germline mutations resulting from modern medicine by tracking mutation rates and genomic locations. Therefore, while it is presently challenging to apply most versions of the precautionary principle to GGE, this difficulty largely stems from knowledge gaps that could be addressed in the future.

Moreover, the precautionary principle does provide relatively clear guidance on one aspect: it suggests preferring certain applications of GGE over others. In particular, the precautionary principles outlined in this article advocate for GGE research aimed at preserving genetic health, enhancing the long-term viability of human populations, or mitigating existential risks, rather than research focused on modifying cosmetic traits or excessively promoting health beyond a sufficient well-being threshold. The latter practices pose unbalanced long-term harm risks to future generations in exchange for short-term gains, while the former do not.

Conclusion:
The precautionary principle is designed to influence decision-making in scenarios where human activities may pose uncertain yet potentially grave threats. This applies perfectly to the ongoing debates around GGE. It is, therefore, surprising that this principle has not garnered more attention in the bioethics discourse surrounding gene editing. Where it has been mentioned, it is often insinuated with little analytical depth that the principle would oppose human germline modification, potentially ruling it out entirely.

We aim to have provided a more nuanced understanding of how various interpretations of the precautionary principle relate to GGE. We argue that, while negative precautionary principles have practical utility in some situations, they contribute little to the policy discussions concerning reproductive GGE. Positive precautionary principles offer more relevant insights. They emphasize the importance of avoiding certain threats, particularly those we tend to undervalue, those that are not well understood, and those potentially impacting a sufficient standard of well-being and health security. Although it is challenging to derive concrete policy recommendations from these interpretations, plausible versions would support GGE in specific contexts, especially where it could address serious genetic mutations or enhance the long-term resilience of human populations. Given that the precautionary principle is predominantly employed against GGE, we believe this perspective is significant.

Much work remains to clarify how the precautionary principle can offer concrete recommendations for GGE. Nevertheless, we hope to have made progress in this article by arguing against outright rejection of the precautionary principle, elucidating its potential role, and highlighting essential questions that must be addressed.