CRISPR, the groundbreaking gene-editing tool of the last decade, has permanently altered the field of genetics for the science world. The tool efficiently targets specific sequences of genetic code and has revolutionized studies on genomes of a plethora of organisms. CRISPR has played an especially vital role in tackling diseases as the technology enables replacing harmful DNA sequences with healthy ones.
The first cell therapy study with CRISPR was conducted just in 2019 to treat Victoria Gray’s sickle cell disease symptoms.1 Sickle cell anemia is an inherited disease that results in the formation of crescent shaped blood cells.2 For the disease’s thousands of victims, these crescent shaped blood cells can inflict episodes of pain by blocking blood flow in the body. This can make normalcy for sickle cell patients extremely challenging and prompt those like Victoria Gray to turn to new methods such as CRISPR gene editing.
Prior to the clinical trial with Gray, the only known cure for sickle cell was a bone marrow transplant, which is where the stem cells responsible for the faulty hemoglobin in sickle cell are found. This process involves killing the stem cells through chemotherapy and replacing them with healthy cells from a donor.3 The main issue with this solution is finding a donor, and the reason why researchers began to experiment with CRISPR as an alternate treatment.
Scientists focused on using CRISPR to edit a fetal hemoglobin gene that would produce enough healthy cells to counter the defective sickle cells. After extracting and editing Gray’s cells with this process, scientists infused billions of modified stem cells back into her body. For patients such as Gray, CRISPR is life changing – she was able to resume her daily activities without the burden that sickle cell brought upon. However, for others, the outcome can be disheartening and even deadly.
In October of 2022, 27-year old Terry Horgan passed away during a study testing similar gene editing techniques to Victoria Gray in hopes of curing his fatal condition of Duchenne muscular dystrophy. The muscle degeneration disease is caused by a gene mutation that prevents dystrophin, a protein important for holding muscles intact, from being produced properly. Researchers at the University of Massachusetts are unsure of the exact details of what caused the death, but considering methodology, speculation points toward CRISPR possibly playing a crucial role.4
Based on what examination finds in the next few months, Terry Horgan’s death may be a large setback in research and investments towards CRISPR gene editing. The situation bears resemblance to the death of Jesse Gelsinger in 1999, which heavily set back the field of gene therapy at the time. Similar to Horgan, Gelsinger volunteered to be a part of a clinical trial that involved new gene therapy methods. Gelsinger had ornithine transcarbamylase deficiency syndrome (OTCD) where ammonia builds up to lethal levels in the blood due to a damaged or missing transcarbamylase enzyme.5 To treat OTCD, researchers developed a harmless cold virus to contain working copies of the OTC gene, which would be injected into the patient and integrate the added gene through infection of cells. While the method caused mild side effects in other patients, the viral vector caused a fatal inflammatory response for Jesse Gelsinger and dismantled the field of gene therapy for its deadly risks.6
After nearly two decades of research, gene therapy slowly overcame its controversy with new policies requiring researchers to be cautious with human subjects.7 However, gene therapy clinical deaths still occur from time to time.8For Horgan’s case, it has called attention to how CRISPR gene therapy methods are still extremely new – and both its other abilities and long term effects are unknown.9 As CRISPR evolves and develops to have new uses, an ignorance towards its capacity to affect the human genome can lead to only more tragic deaths.
CRISPR’s unique ability to edit almost any part of the genome holds great power, and this is what can give rise to several ethical issues. In the same year of Gray’s successful CRISPR cell therapy treatment, Chinese scientist He Jiankui was sentenced to 3 years in prison for inserting genetically modified embryos unknowingly into two women seeking in-vito fertilization.10While he had positive intentions of absolving them of HIV, an immune disease with great danger towards its victims, it is a reminder that CRISPR puts researchers in potentially-concerning positions of control.
The controversy surrounding the case arose from how the volunteers in the study were not fully informed of the genetic modification happening to the embryos, and while it made large strides forward in gene editing, this behavior should not be tolerated due to its unpredictable risk for future generations.11 Additionally, gene editing embryos can easily be exploited for nontherapeutic methods, posing questions of autonomy in light of CRISPR. The case raises questions of who should decide what genes must or should be edited. With the wrong mindset, the abilities of CRISPR can be warped into a modern form of eugenics, embodying the same intentions to remove “undesirable” qualities but with gene editing.
Because of the intense disciplinary action taken in Jiankui’s instance, there has not been another gene editing scandal of that caliber, but this doesn’t mean it cannot happen again. The ethical issues of editing human embryos range from its future unknown effects for the subjects to unnatural creations of mankind. While CRISPR gene editing may seem like it can improve quality of life for an individual, it is nearly impossible to evaluate whether CRISPR could make a substantial impact. In the cases of Gray and Horgan, the risk of CRISPR is understandable as the gene editing methods were utilized to help eradicate diseases they sought treatment for.
This differs from completely eliminating genes and other genetic material that are considered “undesirable,” which would fall under the HIV case with Jiankui. The eugenic mindset may sound harmless, but it is the same that led to forced sterilization and euthanization in WWII to artificially create the Aryan race Nazis desired.12 This method of complete eradication brings forth an ableist mindset that those with disabilities have nothing to contribute to society. However, those with disabilities are human and have equal rights to life and autonomy just as those without them. Additionally, they have redeemable lessons to share and add another level of diversity to civilization. Disabilities give us the ability to explore different perspectives that pave the way towards kindness, empathy, and generosity. These qualities are essential in ensuring our relationships as human beings to one another are respectable. Beyond modern eugenics, CRISPR can pose another problem, which are lines of social inequality.
As research with genetic diseases and CRISPR progresses, a division between those who can afford the treatment and those who must suffer will begin to emerge. For example, to treat a child with spinal muscular atrophy, the cost of a single gene therapy treatment Novartis is upwards to 2 million without insurance.13 With insurance, the price of one treatment is reduced to $10,000, but the number is still extremely unaffordable for most families. Here, the responsibilities fall on companies to make these treatments more affordable or pose a risk of alienating those with disabilities further out from society.
This is not to say that we should do without CRISPR gene therapy, but to recognize the broader health and social effects that exist as much is unknown about the tool. While CRISPR has been able to significantly alter the lives of those who suffer from genetic diseases, it has also been responsible for deaths and exploitation.
We must continue to acknowledge that CRISPR is a privilege full of medical uncertainties. If examined thoughtfully and integrated into the medical field carefully, CRISPR possesses the capacity to cause incredible healing. If not, it may become another point of division – decisions made today that will influence all of our shared tomorrows.
References:
1. Stein, Rob. “First Sickle Cell Patient Treated with CRISPR Gene-Editing Still Thriving.” NPR, NPR, 31 Dec. 2021, https://www.npr.org/sections/health-shots/2021/12/31/1067400512/first-sickle-cell-patient-treated-w ith-crispr-gene-editing-still-thriving.
2. “What Is Sickle Cell Disease?” National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, https://www.nhlbi.nih.gov/health/sickle-cell-disease.
3. BeTheMatch.org. “Sickle Cell Disease (SCD) .” Be The Match, https://bethematch.org/patients-and-families/about-transplant/blood-cancers-and-diseases-treated-by-t ransplant/sickle-cell-disease--scd-/.
4. Ungar, Laura. “Death in US Gene Therapy Study Sparks Search for Answers.” AP NEWS, Associated Press, 4 Nov. 2022, https://apnews.com/article/science-technology-health-business-genetics-79f4a9b76426ec40c367957e3 bb9cf4a.
5. “Ornithine Transcarbamylase Deficiency.” MedlinePlus Genetics , U.S. National Library of Medicine, https://medlineplus.gov/genetics/condition/ornithine-transcarbamylase-deficiency/#causes.
6. Rinder, Meir. “The Death of Jesse Gelsinger, 20 Years Later.” Science History Institute, 16 July 2019, https://www.sciencehistory.org/distillations/the-death-of-jesse-gelsinger-20-years-later. 7. Savulescu, Julian. “Harm, Ethics Committees and the Gene Therapy Death.” Journal of Medical Ethics, Institute of Medical Ethics, 1 June 2001, https://jme.bmj.com/content/27/3/148.
8. Liu, Angus. “2 Deaths after Novartis' Zolgensma Put Gene Therapy's Liver Safety in the Spotlight Once Again.” Fierce Pharma, 12 Aug. 2022, https://www.fiercepharma.com/pharma/two-deaths-after-novartis-zolgensma-bring-gene-therapys-liver -safety-spotlight-again.
9. “The Gene Editor Crispr Won't Fully Fix Sick People Anytime Soon. Here's Why.” Science, https://www.science.org/content/article/gene-editor-crispr-won-t-fully-fix-sick-people-anytime-soon-h ere-s-why.
10. “Chinese Scientist Who Produced Genetically Altered Babies Sentenced to 3 Years in Jail.” Science, https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sent enced-3-years-jail.
11. Lanphier, Edward, et al. “Don’t Edit the Human Germ Line.” Nature, vol. 519, no. 7544, 2015, pp. 410–411., https://doi.org/10.1038/519410a.
12. “Eugenics .” United States Holocaust Memorial Museum, United States Holocaust Memorial Museum, https://encyclopedia.ushmm.org/content/en/article/eugenics.
13. “Paying for CRISPR Cures: The Economics of Genetic Therapies.” Innovative Genomics Institute (IGI), 18 May 2022, https://innovativegenomics.org/news/paying-for-crispr-cures/.