Clinical Germline Genome Editing: When Will Good be Good Enough?

Ensuring experimental outcomes are of the highest clinical caliber is crucial prior to the introduction of germline genome editing. However, if we are to police scientific progress using probability or the potential to go wrong, then we must account for the specious standards of human reproduction. With 15% of clinically recognized pregnancies estimated to end in spontaneous miscarriage within the first trimester, and 25% of all pregnancies ending in miscarriage, human reproduction has a high failure rate. These figures, coupled with the percentage of all births with congenital defects and the number of these who will die in the first year of life, paint two scenarios: one, that evolutionary checkpoints are cruel but critical, and two, that for the seemingly inevitable 3%, or 8 million babies born annually with congenital disorders, perhaps more must be done for prevention, when methods exist for prediction. Unifying progress in three coevolving technologies—assisted reproduction, genome editing, and genome sequencing—could produce revolutionary clinical changes in the harsh global statistics of hereditary disease. A historical perspective on the rocky foundations upon which IVF was built suggests that lessons should be learned from the misalignment of research and clinical practice due to funding and research restrictions. At present, it seems likely that history will repeat itself, and that progress in research will be hampered by hypocritical hesitation.