CRISPR process

CRISPR Mechanism

Although the conditioning of embryos depicted in Aldous Huxley’s “Brave New World” remains science fiction, developments in gene editing have raised troubling bioethical dilemmas. Targeted gene editing has recently been made possible through clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, which allows researchers to generate RNA-guided nucleases, such as Cas9, that can rapidly and efficiently modify genes in a large variety of cell types and organisms.1 Researchers have already begun to employ CRISPR-Cas9 for many purposes, including rapidly genetically engineering rodents to study diseases and growing human-like organs in pigs for possible transplant.

Gene editing research could lead to significant medical and environmental benefits. Experts anticipate ex vivo therapies could help treat genetic diseases such as sickle cell, hemophilia, muscular dystrophy, and cystic fibrosis. For sickle cell, instead of implanting donor cells in a difficult bone marrow transplant, health professionals could use CRISPR to genetically correct the blood cells of patients.2 Cells would be extracted, manipulated, and tested before being returned to the body. Similar approaches could allow the T cells of cancer patients to be retrofitted with antigen receptors for specific cancer mutations, or the immune cells of HIV patients to be rendered infection-resistant. Although in vivo editing is more difficult, applications might include the treatment of some nerve and eye conditions. Gene editing could also be used to eliminate invasive plants, which can disrupt ecosystems, or make it harder for malarial mosquitoes to breed and carry disease. In agriculture, CRISPR could be utilized to modify organisms that have previously resisted genetic engineering, allowing the growth of new GMOs. In addition, scientists are using edited nerve cells to study the mechanisms behind neurological disorders.3

Gene editing research… could help treat genetic diseases such as sickle cell, hemophilia, muscular dystrophy, and cystic fibrosis.

But the technology ignited controversy in April, when scientists in China carried out the first gene editing experiment using the DNA of human embryos. They attempted to modify the gene that causes β-thalassemia, a serious blood disorder, when mutated.4 In Britain, regulators have received requests to gene-edit human embryos to study early development.5 While the National Institutes of Health has banned gene editing of human embryos in the United States since 1996, the National Academy of Sciences (NAS) will convene an international summit in December to explore the scientific and ethical quandaries associated with human gene-editing research. The largest issue will be the permissibility of altering human heredity by editing embryonic genes.6

CRISPR technology is not currently safe or developed enough — for example, the Chinese researchers found that embryonic gene editing, while sometimes successful, often did not work or produced unintended and harmful mutations, due to the action of nucleases at locations other than those targeted.7 Nonetheless, the pre-implantation correction of genetic anomalies in embryos produced through in vitro fertilization (IVF) remains a likely long-term possibility.89 The inability for a future child to consent to genetic tinkering complicates ethical judgments about what alterations parents could have the right to make. The stakes are high — while CRISPR has the potential to vastly improve the life of a person who would otherwise face a genetic disorder, that child’s own children could would be affected by any germline gene editing.

I suspect that many people would find two aspects of human gene editing intuitively worrisome. First, exercising that amount of control over human life resembles “playing God” in a disturbing way. Second, making genetic “improvements” not intended to cure harmful abnormalities seems problematic, even if such alterations became safe and inexpensive.

I believe there is some middle ground. Parents are already permitted to make some rudimentary “genetic choices” about the sort of children they will raise. For instance, in the IVF process, preimplantation genetic diagnosis (PGD) screens embryos before they are transferred to the uterus. Couples can potentially select embryos unaffected by genetic or chromosomal disorders.10 Unfortunately, when several genes are involved in a disease, most embryos need to be discarded. Gene editing could greatly increase the odds of getting a healthy embryo.11 Another example is mitochondrial DNA donation, an IVF technique that replaces defective DNA from the mother with equivalent DNA from another woman, which recently became legal in Britain.

Gene editing is a morally legitimate way of avoiding true human defects or diseases — preventing massive suffering and extending lifespans — but not merely satisfying parental preferences. It seems wrong for parents to use their position of comparative power to manipulate their children, before they are incapable of agreement, to accommodate their own desires. It also seems unethical to make modifications that might make someone’s life easier just because of social attitudes or constructions. While these examples are far-fetched, it would be repugnant to attempt to produce a child with lighter skin, a different gender, or more desirable physical characteristics. In contrast, removing genes that might increase the likelihood of breast cancer or early-onset Alzheimer’s seems acceptable. This is because, except in the most clear-cut cases, it is probably wrong for others to impose subjective judgments about what constitutes a better life, one that is more “worth” living, on another person. Some gene editing could involve changing features very salient to a person’s future identity. It is odd to think that basically “ending” the lives of particular “people” and replacing them by genetically altering embryos could easily be justified. Parents can probably request editing that would allow their children to become purposive and independent agents — constitutive human characteristics that many genetic disorders would affect — but making most other decisions for children would egregiously violate their autonomy. No parent has the right to a child with a particular height or eye color.

In addition to helping prevent genetic disorders, embryonic gene editing could help answer other scientific questions about human development, and produce stem cells that could act as models for drug testing and disease interventions. Such work is contentious, but it is worth noting that embryos involved in this research are not viable for live births.12 The practice is no worse than what happens in IVF when non-viable embryos are discarded.

My loose sketch cannot do full justice to the complexity of the gene editing debate. After the NAS conference, gene editing research will hopefully proceed with a greater consciousness of the bioethical issues involved. Overall, there is reason for cautious optimism about the technology.

  1. Sander, J., & Joung, J. (2014, March 14). CRISPR-Cas systems for editing, regulating and targeting genomes. Nature Biotechnology, 32(4), 347-355.
  2. Niiler, E. (2015, October 6). Science Would Like Some Rules for Genome Editing, Please. Wired Magazine.
  3. Neergaard, L. (2015, October 9). Gene editing: Research spurs debate over promise vs. ethics. Associated Press.
  4. Kelland, K. (2015, September 2). Medical specialists urge more debate on gene-editing technology. Reuters.
  5. Gammon, K. (2014, November 13). Gene therapy: Editorial control. Nature, 515, S11-S13.
  6. The Age of the Red Pen; Genome Editing. (2015, August 22). The Economist.
  7. Regalado, A. (2015, April 22). Chinese Researchers Use Genome Editing on Human Embryos. MIT Technology Review.
  8. Gallagher, J. (2015, January 19). ‘Designer babies’ debate should start, scientists say. BBC News.
  9. Corbyn, Z. (2015, May 10). Crispr: Is it a good idea to ‘upgrade’ our DNA? The Guardian.
  10. Preimplantation Genetic Diagnosis (Embryo Screening). (n.d.). Penn Medicine.
  11. Cyranoski, D. (2015, March 18). Ethics of embryo editing divides scientists. Nature, 519, 272.
  12. Cyranoski, D., & Reardon, S. (2015, April 29). Human Embryo Editing Sparks Epic Ethical Debate. Nature, 520 593-595.