Should we edit our genes?
Human gene editing is moving increasingly further away from science fiction, especially with the advent of CRISPR. The idea of using CRISPR for the purposes of gene editing was first described by a group of scientists led by Doudna and Charpentier in 2012.1,2 Since then, this technology has already shown promise through its use in mice and monkeys. Most recently, a group from China has successfully used CRISPR to modify the genes of human embryos in the lab.3-5 Although CRISPR has great potential to develop into a gene therapy that could almost eliminate serious and fatal genetic diseases, careful consideration must be taken in how this tool is used and regulated in laboratories across the world. Without a doubt, CRISPR has great potential in becoming a revolutionary tool, but is it too soon to start altering the human genome?
Genome engineering is not a new idea in the realm of research. In fact, gene manipulation technologies have been used for years to alter the genomes of mice, fruit flies, and other organisms.6 These methods include site-directed zinc finger nucleases (ZFNs) and transcription activator-like effectors (TALEs). CRISPR differs from these past methods in that it is more efficient, relatively simpler, and less expensive, making its use in humans more feasible.1
There are, however, some technical limitations with CRISPR that have yet to be overcome. The Cas9 nuclease component of this system, which is involved in recognizing and cleaving DNA at the sites targeted for modification, does not have perfect DNA recognition. This imperfect recognition can lead to off-target effects in which DNA is unintentionally cleaved at different sites within the genome.7 Although research into improving the specificity of the Cas9 nuclease is underway, this technology still needs more investigation before it can be safely used beyond the research laboratory.8,9
With further investigation and refinement, CRISPR technology has the potential to develop into two distinct clinical applications: germline and somatic human gene editing. Germline gene editing involves altering the DNA in sperm and egg cells, with their progenitor cells or early embryos to be used in reproduction. Although the changes introduced through this technique could prevent the transmission of genetic diseases to the next generation, the risk of errors and unintended effects in future generations is unknown. Somatic gene editing raises fewer ethical and social concerns because it involves manipulating the genetic material of body cells in already existing patients. This type of human gene editing has the potential to treat a myriad of diseases including some blood disorders, immune deficiencies, and cancers.10
Germline gene editing has recently stirred debate with its proposed use in assisted reproductive technologies, such as in vitro fertilization (IVF). Is it ethical for parents to give consent for the editing of their unborn offspring’s genes? Where do we draw the line between gene therapy and genetic enhancement? Parents currently have the power to use reproductive genetic testing and screening, which can be helpful for parents at risk of transmitting a heritable disease to their children or for older women who are at risk of having a child with a chromosomal condition. Genetic screening of embryos, however, has the potential to be used to select traits for non-medical purposes. Chrissy Teigen, an American model, made headlines when it was revealed that she and her husband purposely chose a female embryo during IVF. This type of sexual selection is legal in parts of the United States; however, Canadian law prohibits couples undergoing IVF to predetermine the sex of their children unless there is family history of sex-linked disorders, such as hemophilia (Figure 1).11
Using CRISPR for human gene editing also raises the question of where the divide between diversity and disability lies. Some individuals may view a particular trait as a disease, while others may see this trait simply as variation in the human population. For example, not all deaf people consider themselves disabled. Some deaf people would go so far as to choose embryos during IVF in order to ensure that their children will be deaf.12,13 The genetic variants that make these individuals deaf is not something that they would likely want to change using CRISPR, especially in their germline cells. This is not to say that genetic diseases cannot be debilitating; individuals with life-threatening hereditary diseases such as cystic fibrosis and Huntington’s disease could greatly benefit from somatic gene editing.14 Gene therapy in the form of CRISPR could offer a treatment or even a cure for these individuals beyond symptom management.
Inconsistencies across the globe can make it difficult to predict how CRISPR technology will develop. Many countries have put a ban on human germline gene modification, but this practice is not banned at the legislative level in every country of the world. Canada, along with Bulgaria, Belgium, Denmark, Sweden, and the Czech Republic have laws in place which ban all human germline gene modification.14 The United States is unique in that human germline gene editing is under a temporary moratorium as per guidelines set out by the FDA and NIH until the technology is further investigated.14 Other countries such as China, India, Ireland, and Japan ban the modification of germline genes based on guidelines, which are less enforced than laws.14
The discussion surrounding CRISPR and human gene editing has just begun, and many questions remain unanswered. Can the technical hurdles involved with CRISPR be overcome with more research? How can the effect of this technology on future generations be studied? What will the implementation of this type of medical treatment mean for disability rights? Researchers should not be held back in investigating CRISPR technology, but at the same time, they should proceed with caution. Before human gene editing can become a reality, it is imperative that the scientific, social, and ethical implications involved be discussed at length.
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10. Olson S. International Summit on Human Gene Editing: A Global Discussion. Washington (DC) 2016.
11. Rose LL. Chrissy Teigen's choice of female embryo re-sparks sex selection debate. CTV News 2016.
12. Hayden EC. Should you edit your children’s genes? Nature. 2016;530:402-405.
13. Sanghavi DM. Wanting Babies Like Themselves, Some Parents Choose Genetic Defects. 2006; http://www.nytimes.com/2006/12/05/health/05essa.html?_r=0.
14. Araki M, Ishii T. International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reprod Biol Endocrin. 2014;12:1-12.
Cite This Article:
Peacock E., Zheng K., Chan G., Ho J. Should we edit our genes? Illustrated by B. Sharma. Rare Disease Review. July 2017. DOI:10.13140/RG.2.2.10629.55521.