The Discovery, Application, and Ethical Debate of CRISPR/Cas9

by Gabriel Brutico, GCSOM, MBS 2019
Mentor: Dr. Gregory Shanower, PhD

I recently wrote a review paper on CRISPR/Cas9 and its potential applications and implications. Originally, I had very little understanding of the technique, especially with regard to its mechanism and rich history.

CRISPR/Cas9, or just CRISPR, is a gene-editing tool that was discovered in the 1990s from research conducted on bacteria and archaea. Since its discovery, it has been developed as a versatile technique for studying all types of organisms, including people. In prokaryotes, CRISPR functions as part of the adaptive immune response, which is unique because it can be inherited. In order to gain a certain adaptation, the prokaryote or its ancestors must be exposed to the virus. Some portions of the viral DNA are recognized by the prokaryote and incorporated into their genomes at the CRISPR loci. These new DNA segments are known as spacer regions, and will be transcribed following future encounters from the same virus. The spacer region RNA along with tracrRNA and Cas proteins bind to the viral DNA and cause its degradation. Aside from research on mouse models and human cells in vitro, the technique has mostly been implanted in improving the growth and yield of different crops.

Though CRISPRs implementation into modern medicine has the potential to be beneficial to the world’s most complicated conditions, more recent research has sparked a lot of debate on the ethics and potential risks involved. Some researchers are in support of further testing of CRISPR in animals and people, claiming that we have moral obligations to seek out and implement new techniques that could decrease the burden of disease. Others have voiced a more cautious approach, insisting that CRISPR research in human cells, specifically embryos, be banned from publication and use due to the potential negative consequences of the widespread use of a gene-editing tool.
As someone who enjoys learning about all aspects of science, especially the historical development of different techniques and subjects, with chemistry and astronomy being my most favorite history lessons, I can recall previous discoveries that were extraordinarily beneficial and can envision the similar impact that CRISPR could have on combatting human disease. There are many risks to consider however, including the use of CRISPR for nonmedical purposes. CRISPR has been implemented in decreasing mosquito populations by genetically altering their DNA to cause only male offspring. As such, some argue that it is reasonable to assume that CRISPR could be used to produce disease-carrying insects as a form of biological warfare.

Regardless of whether countries eventually ban or advocate for its use in medicine, it will likely be used in some cases for altering traits other than those involved in a disease, especially in countries with less laws on medical and research practice. As such, it may be possible for people to receive CRISPR treatment by traveling out of their country if the laws prohibit its use. This would be similar to how some people currently travel out of the U.S. to receive medical procedures, though I would agree that this is a seldom occurrence. CRISPR has been shown to be applicable to some of the most challenging conditions, such as HIV/AIDS and cancer, and so research on its medical applications requires expansion and refinement to decrease its limitations caused by unintended DNA alterations. As such, its use as a medical treatment should proceed with caution after further testing and trials, and it should be implemented with the same ethical standards as other treatments. With implementation, researchers and physicians need to be mindful of the ethical principles of beneficence, nonmaleficence, respect, and justice in treating patients, and there needs to be quick action against those using CRISPR for nonmedically beneficial purposes. Fines and sentencing should be daunting for misuse because of the ethical implications caused by changing non-medically relevant traits before birth, and because of its potential to cause unintended mutations.

Whether future laws allow or prohibit CRISPR use, there will likely be someone abusing the power of CRISPR as a gene-editing tool, especially in countries that have little regulation. It is because of this and its vast potential for treating complex diseases that I advocate for its continued research and future implementation in people. I would compare CRISPRs potential to that of vaccines. When immunizations were first developed, they too had unintended consequences, but have proven to change the course of history and human disease. As such, researchers, physicians, and policy makers should be mindful of the negative consequences, but proceed with the highest standard of ethics following strong evidence.