Improvements in the efficacy of the CRISPR-associated (Cas) 9 system for gene editing, coupled with its low cost and ease of use, will increase the number of people using it and the ways in which it will be used, five US and Canadian experts said in a Q&A published in Clinical Chemistry. However, the panel also identified several ethical concerns related to its widespread use.
“The democratization of the technology—by making it cheap and easy enough for poorly funded amateurs—could have vast effects by making it harder for anyone to control,” said Henry T. Greely, JD, from Stanford University in Palo Alto, California. Charis Thompson, PhD, from the University of California, Berkeley, echoed his concerns. “The fact that nearly every academic and industry laboratory—and some civilian-run laboratories and garage spaces—can participate in this work relatively easily changes everything: how fast it is being improved; how democratic participation is; and how quickly good and bad uses could be developed and spread.”
The system still has limitations, panelists said. These include very few simultaneous changes per cell, inefficient homology-directed repair (HDR) to nonhomologous end-joining (NHEJ) ratio, and issues around efficient delivery to all cells or to a precise subset, said George M. Church, PhD, from Harvard Medical School in Boston.
Francoise Baylis, PhD, from Dalhousie University in Halifax, Nova Scotia, listed CRISPR users as another limitation, given the fierce competition the science is expected to seed among research teams, for-profit companies, and nation states. She also addressed the potential consequences of off-target effects, including lack of specificity and incomplete targeting. These, she said, “could have devastating effects on patients.” Gerold Schmitt-Ulms, PhD, from the University of Toronto, however, pointed to several improvements in the technology that should mitigate this concern.
The panelists had divergent views on the ethical issues regarding the use of CRISPR in humans. Gene editing in humans is not new, said Church. “It is not just used in human cells or embryos (as CRISPR has), but also in approved clinical trials (in human adults and children).”
Thompson agreed that appropriately consented human embryos can be gene edited to learn more about human biology, “but edited human embryos should not at this point be implanted in any woman’s womb with the intention of establishing a pregnancy,” she said. Schmitt-Ulms, however, argued the widespread fear that these experiments are the precursor to inevitable future uses of the technology in human genome engineering seems “overblown.”
If, however, CRISPR becomes completely safe and effective, several panelists predicted it could be used to edit somatic cells of people or fetuses and embryos to prevent heritable diseases, even to edit the germline to prevent any future transmission of heritable diseases.
Several panelists thought the technology would one day be called into action for eugenic reasons (improving appearance and intellectual capacity, for instance), a use to which most were adamantly opposed. As Baylis said: “I have argued elsewhere, and continue to believe, that human genetic enhancements are inevitable. This perspective is informed by a particular view of human nature having to do with capitalism, heedless liberalism, drive for knowledge, a desire to outperform, and a fair amount of hubris allowing us to believe that the future is ours for the shaping.”
Schmitt-Ulms said: “I am categorically opposed to the use of this technology in humans for the pursuit of nonmedical objectives, and I am not aware of any reasonable person who would advocate it.”
Rather, panelists highlighted more appropriate clinical and societal applications of the system in the future. These included reducing risk to embryos and lowering the number of induced and spontaneous abortions; improving the ability to feed and provide energy for humans while preserving or even improving the environment; ameliorating classic gene therapy; reducing single-gene, lethal defects or even eradicating certain fatal diseases; speeding drug discovery; and facilitating translational research by modeling critical aspects of diseases in eukaryotic cells or model organisms.
One concern, several of the panelists said, is that the technology would be limited only to wealthy nations and individuals that can afford it. “It is a sad truism that technological advancements generally tend to benefit wealthier segments of societies first,” said Schmitt-Ulms. “This technology will be no exception, and it is to be expected that access to certain CRISPR-Cas9 applications will first become available in places that have a well-functioning healthcare system.”