Reactions to the National Academies/Royal Society Report on Heritable Human Genome Editing

The clinical applicability of porcine xenotransplantation-a long-investigated alternative to the scarce availability of human organs for patients with organ failure-is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated PERVs. Here, using a combination of CRISPR-Cas9 and transposon technologies, we show that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans. The engineered pigs exhibit normal physiology, fertility and germline transmission of the 13 genes and 42 alleles edited. Using in vitro assays, we show that cells from the engineered pigs are resistant to human humoral rejection, cell-mediated damage and pathogenesis associated with dysregulated coagulation. The extensive genome engineering of pigs for greater compatibility with the human immune system may eventually enable safe and effective porcine xenotransplantation.

Abstract The extraordinary wave of genomic-engineering innovation, driven by CRISPR-Cas9, has sparked worldwide scientific and ethical uncertainty. Great concern has arisen across the globe about whether heritable genome editing should be permissible in humans—that is, whether it is morally acceptable to modify genomic material such that the “edit” is transferable to future generations. Here I examine 61 ethics statements released by the international community within the past 3 years about this controversial issue and consider the statements' overarching positions and limitations. Despite their inability to fully address all important considerations, many of the statements may advance debate and national and international law and public policy.