Abstract
In November, 2018, Dr. Jiankui He reported in the popular press that twin infant girls had been born after having undergone gene editing during the embryonic period with the intent of rendering them genetically resistant to human immunodeficiency virus infection. 1 While the scientific validity of this report has not yet been independently confirmed, the worldwide reaction to the ethical dimensions of this announcement has been overwhelmingly negative.
In April 2019, an independent group of biomedical scientists, including myself and other members of our senior editorial team, sent an open letter to the U.S. Secretary of Health and Human Services, Alex Azar II, regarding the reported actions of Dr. He. The letter condemned these actions and furthermore called for “a binding global moratorium limiting clinical testing of germline gene editing in humans.” 2 The letter went on to advocate for improved mechanisms to report violations of this moratorium. Specifically, the use of gene editing on embryos that are subsequently implanted with the intent of establishing a pregnancy would be strictly forbidden.
Historically, the two foundational principles regarding gene therapy are (1) that it should be used only to treat disease and not for enhancement, and (2) that it should only be used on somatic cells and not to alter the germline of the human species. Based on the second of those foundational principles, embryo editing would be prohibited, as was reaffirmed in 2015 when the first non-reproductive human embryo editing was reported. 3
Furthermore, there is widespread consensus that the accuracy and reproducibility of gene editing is not sufficient to ensure the safety of editing an entire human embryo. The use of editing in the context of a limited organ or cell type among somatic cells would intrinsically be less hazardous, and thus would always have a more favorable risk–benefit ratio. The current consensus is that the context in which embryo editing could be ethically performed would be that of in vitro fertilization, a context that would enable pre-implantation genetic testing as a means to select unaffected embryos from a mating of two parents whose genetic carrier status puts the pregnancy at risk.
Finally, we must consider the fact that reckless actions such as those of Dr. He put the public trust in the biomedical research community at risk at a time when appropriate use of gene therapy and gene editing is providing hope for patients with previously incurable genetic disease. What is called for at present is not a rush to embryo gene editing or even to systemic gene editing. Rather, we advocate a focus on research to improve the tools of gene editing in order to improve their efficiency and molecular fidelity while moving forward with clinical applications for which the current level of fidelity is sufficient to ensure safe and effective therapeutic outcomes. Examples would be any of a number of ex vivo gene editing approaches (such as chimeric antigen receptor T-cell or hematopoietic stem-cell editing) or those in vivo targets that are relatively small and sequestered (such as retinal photoreceptors). In this context, gene editing can move forward within the broader gene therapy context without creating any unwarranted hazards to patients or human society.