Counterpoint: The Potential Harms of Human Gene Editing Using CRISPR-Cas9.

Abstract

The anticipated benefits of human gene editing with the use of CRISPR (clustered interspaced short palindromic repeats)-Cas9 are both familiar and contested. First and foremost is the expectation of cures for blood disorders, lung diseases, cancers, and other maladies as clinician-scientists master various insertion, disruption, and deletion techniques. In addition to these potential therapeutic benefits, for some, there are the potential benefits of human enhancement as investigators learn to modify specific genetic traits in an effort to improve healthy individuals. Importantly, these proximate and distant potential benefits might be obtained through somatic cell or germ line gene modification. With germ line gene modification (which involves inserting, deleting, or replacing the DNA of human sperm, eggs, or embryos), there is the added potential benefit that changes made to the human genome (especially those aimed at correcting disease-causing and sometimes life-limiting genetic mutations) will be inherited by future generations. This would obviate the need for repeat somatic cell modifications from one generation to the next. The potential benefits of gene editing, however, are neither guaranteed nor risk-free. The potential harms include off-target changes (as might happen with the inactivation of essential genes), the inappropriate activation of cancer-causing genes, and the rearrangement of chromosomes. Additionally, there are the risks of on-target changes with unintended consequences, the creation of mosaics of altered and unaltered cells, and the introduction of changes that generate an immune response. In addition to these potential medical harms, there are also potential social harms. There is, for example, the risk that the introduction and eventual wide utilization of gene editing technology will exacerbate existing inequalities resulting in human rights abuses, a new wave of eugenics, increased discrimination and increased stigmatization. As such, the overarching risks with human gene editing by use of CRISPR-Cas9 are two-fold. First, there is the risk …