Ethics of gene therapy.

Abstract

CRISPR-Cas systems, base editing, and prime editing have made precise genetic interventions possible, and several approved therapies now treat monogenic disorders that were previously untreatable. Heritable genome editing remains ethically contested. We argue that heritable interventions should not be treated as a single category subject to uniform prohibition. We distinguish three targets: catastrophic monogenic disorders, polygenic risk reduction, and non-disease trait enhancement. For catastrophic monogenic conditions in which preimplantation selection cannot yield unaffected embryos, heritable editing is permissible, and the duty of beneficence toward future persons may require it. When the alternative is certain severe suffering or early death, the expected benefits clearly outweigh the risks. For polygenic interventions, current scientific uncertainty makes clinical application premature: predictive validity remains insufficient and pleiotropic effects are poorly understood. For enhancement, the case is weaker still. Some of its benefits are positional; the risks of social stratification are significant; and the evidence base is absent. We conclude that governance frameworks should permit what the evidence supports under stringent safeguards and prohibit what it does not. The central ethical questions concern welfare, not appeals to nature or abstract notions of dignity. Where the evidence warrants it, failing to pursue heritable gene therapy responsibly may itself be an ethical failure. We outline a translational pathway for ethical germline gene editing.