Human germline editing in the era of CRISPR-Cas: risk and uncertainty, inter-generational responsibility, therapeutic legitimacy

Abstract

Background: Clustered Regularly Interspaced Short Palindromic Repeats-associated (CRISPR-Cas) technology may allow for efficient and highly targeted gene editing in single-cell embryos. This possibility brings human germline editing into the focus of ethical and legal debates again.

Main body: Against this background, we explore essential ethical and legal questions of interventions into the human germline by means of CRISPR-Cas: How should issues of risk and uncertainty be handled? What responsibilities arise regarding future generations? Under which conditions can germline editing measures be therapeutically legitimized? For this purpose, we refer to a scenario anticipating potential further development in CRISPR-Cas technology implying improved accuracy and exclusion of germline transmission to future generations. We show that, if certain concepts regarding germline editing are clarified, under such conditions a categorical prohibition of one-generation germline editing of single-cell embryos appears not to be ethically or legally justifiable.

Conclusion: These findings are important prerequisites for the international debate on the ethical and legal justification of germline interventions in the human embryo as well as for the harmonization of international legal standards.

Keywords: Germline therapy; Human embryos; Responsibility for future generations; Risks; Therapeutic legitimization.

Fig. 1

Scenario 1. Hereditary outcomes of CRISPR-Cas mediated correction at the CFTR site (WT: wild-type allele; M: mutant allele)

Fig. 2

Scenario 2. “One-generation genome editing” (AAVS1: Adeno-Associated Virus Integration Site 1; WT: wild-type allele; M: mutant allele)