Table 1 Summary of simplified ethical arguments for and against HPE

Consistency²

Reducing the incidence of polygenic diseases is a recognized global priority. Reducing the underlying genetic risk is similar to reducing environmental contributors to polygenic diseases.

This does not apply if the side effects of genetic interventions are different from those of environmental interventions. We lack clear evidence that reducing genetic risks has the same overall effect as reducing environmental risks. Germline gene editing introduces heritable changes; therefore, the bar for safety needs to be set higher.

Rights³⁷

Future generations have the right to health. This implies a right to a low risk of polygenic diseases.

Germline genetic interventions violate the rights of future generations to make choices about their own bodies, including their genomes.

Distributive justice³⁸

By reducing the incidence of polygenic diseases, HPE could reduce the strain on medical resources and make them more available to others.

This depends on the number of people who use HPE, and requires appropriately designed health systems to ensure that savings from HPE are appropriately redistributed through the health system. In addition, non-genetic interventions to promote health may better benefit the worst off.

Welfare³⁹

The use of HPE can help maximize the well-being of future generations, both by lowering the risk of disease and by enhancing non-disease traits (that is, enhancement).

Using HPE to increase individual well-being through a market exacerbates injustice and inequality and reduces valuable forms of diversity. Currently, genetic interventions are extremely expensive. Changes in the environment and non-genetic interventions may be cheaper and more accessible.

Ethical arguments against HPE

Possible response

Inequality³

HPE could deepen inequalities in future societies. Disease risk could be concentrated in those with lower socio-economic groups who are already most disadvantaged.

This depends on how HPE is regulated and made available. There are ways to implement HPE, where it reduces existing inequalities by prioritizing the worst off, as should be done with all medical treatments (for example, through public funding).

Safety

HPE introduces new combinations of variants that can be dangerous or unsafe. It would be unethical to impose this uncertain risk on future generations.

It is vital that any use of HPE be supported by rigorous safety data and have a clear justification²³ through a risk/benefit balance. In addition, natural reproduction generates new combinations of variants. One strategy is to limit HPE to variant combinations already seen in existing populations.

Enhancement⁴⁰

HPE can be used to select non-disease traits (for example, intelligence or athletic ability) and produce human phenotypes that we have never seen before. This may cause future generations to be very different from the current generation.

HPE for non-disease traits can be potentially controlled through regulations, which limit its purpose to reducing risk of disease and promoting well-being.

Diversity⁴¹

Widespread use of HPE can reduce the valuable forms of diversity.

Targeting polygenic traits may have a limited effect on genetic diversity. The value of genetic diversity should be weighed against other values, such as individual well-being and health.

Means matter⁴²

HPE may cause us to overlook other approaches for reducing polygenic diseases. For example, preventing heart disease through HPE may reduce efforts to improve diet and exercise.

This is not an either/or option. Society can prioritize environmental measures that are low cost and broadly beneficial while also lowering genetic risk.

Design⁴³

Human polygenic traits have been carefully designed through natural selection. The use of HPE to alter human bodies disrupts this design and leads to harm.

Human bodies have mutations that predispose them to diseases and disadvantages. Evolution is blind to human suffering. The fact that so many people suffer from polygenic diseases shows the need to intervene and reduce suffering.

Non-identity⁴⁴

Large-scale polygenic editing may be ‘identity-alteringʼ. The non-identity problem is a puzzle in ethics when our current actions might change who is born in the future. It can be hard to specify how these actions can be harmful to people who would otherwise not have existed. This means that it does not benefit individuals but rather changes who exists.

Many public health interventions may also be identity-altering. An example is delaying conception to avoid Zika infection⁴⁵, which changes the timing of conception and, thus, the identity of the sperm and egg creating a child. However, this does not mean that we should not consider the well-being of those who come into existence, even if the alternative is non-existence. At most, this indicates that we should give lower priority to HPE than to identity-preserving medical interventions (for example, antibiotics and surgery).

Expressivist⁴⁶

The use of HPE to eliminate variants linked to a disease or disadvantage expresses a negative attitude towards individuals living with that disease or disadvantage.

HPE does not need to express a negative attitude towards people, but rather towards diseases or traits. We should ensure that support is maintained for those who do not receive gene editing.

Reduced resources⁴⁷

The use of HPE to eliminate variants linked to a disease or disadvantage may reduce support for others living with conditions, who cannot or do not wish to obtain access to HPE.

This is not an inevitable consequence of HPE. In some cases, reducing the incidence of a disease will result in more resources available to those who remain with conditions. For example, a reduction in the incidence of beta-thalassaemia in Cyprus due to carrier screening programmes resulted in more resources available to the remaining patients⁴⁸.