For Victoria Gray, a common cold used to send her into a panic of whether she’d end up in a hospital because of her sickle cell anemia she was diagnosed with as a baby. According to the Mayo Clinic, sickle cell anemia is an inherited disorder that impacts the shape of red blood cells that are responsible for the transport of oxygen throughout the body [1]. Gray has been given a life changing CRISPR gene editing treatment that alleviates the effects of the disease. Now, Gray is able to live her life without pain medication and late-night hospital visits—all because of this new technological development and study [2]. However, CRISPR may present unknown challenges, such as ethical concerns surrounding bodily autonomy, an emphasis on Western perspective, and the possibility of detrimental side effects such as other congenital illnesses if used in utero.
There is currently no cure for the condition, instead just ways to manage symptoms. Those with sickle cell anemia experience severe episodes of pain called ‘pain crises,’ anemia, swelling of hands and feet, frequent infection, delayed growth, and problems with vision [1]. The severity of these symptoms creates a high demand for researching a cure—with 100,000 Americans’ health being compromised by the disease [3].
On a genetic level, sickle cell anemia results from a single point substitution, which CRISPR corrects with extreme precision depending on this specific mutation. [4]. CRISPR gene editing is now being explored as a solution to alleviate the symptoms of sickle cell anemia with the Nobel prize-winning ability to change, disrupt, delete, or correct regions of DNA [4].
Multiple studies performed by Vertex Pharmaceuticals Inc, in collaboration with CRISPR Therapeutics and Stanford Medicine, have made CRISPR able to be administered in a single injection. Stem cells, which are unique in their ability to differentiate into a variety of specialized cells, are taken up from the patient, edited with CRISPR technology, and then injected back into the patient to produce normal, functional cells. The mutation in sickle cell affects the shape of hemoglobin, which shuttles oxygen from the lungs to tissues, and can be restored to its functional state and wild type shape. The editing targets defective cells with the DNA sickle cell anemia mutation by cutting the defective DNA and delivering the correct amino acid to the sequence [5]. Vertex Pharmaceuticals Inc hopes to get this treatment approved by the FDA in late 2023 or 2024 [2].
This single-injection approach to CRISPR can provide a more cost-effective and accessible form of treatment for populations living in poverty as an alternative to expenses of pain management, blood transfusions and frequent hospitalizations. CRISPR can also replace the monthly infusions of donor red blood cells that, according to the Red Cross, utilize 16 million units of blood every year [6]. Infusions are not only painful, but reducing their frequency can alleviate the strain of recent blood shortages as a result of the coronavirus pandemic, with fewer blood donors now more than ever. Therefore, CRISPR technology can eventually lower costs for the healthcare expenditures that can be allocated to other research initiatives.
CRISPR also provides hope for treatment both during and after pregnancy for sickle cell anemia. According to a paper published in the National Library of Medicine, other gene therapies like germline therapies prevent disease through CRISPR injection into eggs and sperm. However, germline therapies are unknown in how they impact fetal development. [7].
When used in utero, one study published in the peer-reviewed medical journal Cell found that Cas9—the enzyme used to cut the DNA—can cause major chromosome loss [8]. This potential outcome could lead to symptoms and diseases worse than what the patient originally had – which poses notable risk to those accepting treatment. If done in utero, this could lead to other congenital disorders [9] leading to the question of if the benefits of experimental treatment, like living pain free, is worth the potential risk of irreversible disability.
In addition, researchers have a very poor understanding of how cells are affected by CRISPR technology. With CRISPR, although created with the intention to be precise, it is often unknown if the target mutation was effectively removed or edited. The types of repair mechanisms that are initiated with CRISPR are not always accurate to create other point mutations. Alternatively, CRISPR uses generic sequences to identify the target mutation. If these nucleotides are very common and can be found in other places of the genome, CRISPR may edit the wrong gene.
With these potential dangers, the patient is not the only one to be considered when providing treatment. We must instead weigh the potential dangers of chromosome damage or loss on the quality of life of the multiple generations impacted by the treatment. Ultimately, CRISPR gives the fetus no choice in whether to accept the treatment, whereas CRISPR modifications made in adults allow the individual to express their bodily and medical autonomy. This brings into question the role of medicine and how it designates sovereignty.
CRISPR also poses ethical concerns due to its ability to preferably pick one gene over another. The new term ‘CRISPR babies’ has developed from concerns for human gene-editing allowing for customized children. Instead of just addressing genetic diseases, many criticize the potential for genetically modifying children to skew the natural variation that comes with sexual reproduction for the ‘ideal,’ ‘healthy’ child. Definitions of health and ‘model children’ may create artificial selection driven by prejudice that unequally values different racial identities. When heterozygous, sickle cell anemia creates a natural resistance to malaria which is prevalent in warm climates, like Africa [10]. Just the treatment of sickle cell anemia based on Western ideas of ‘health’ may create an even larger health crisis and mismanagement of health resources for malaria in Africa. So, although CRISPR can improve well-being and reverse the effects of sickle cell anemia, if done in gestation, it could produce even more vulnerability in African populations. Curing sickle cell anemia may reduce this heterozygosity that presents advantages for survival which would make them more at risk for the deadly effects of malaria. Hence, will CRISPR be used to relieve the symptoms of individuals suffering from sickle-cell, or creating another cover for mismanaged and racialized healthcare?
There are not only unknown risks on the biological level, but also the socal level for future disease applications. However, for the immediate future, this technology could present an exciting step forward for those who suffer and live in fear of viruses and simple discomforts the general population face. This technology—despite its many unknowns and risks—could act as a step in alleviating suffering of many health-compromised populations by providing an efficient, cost-effective treatment alternative.
However, the remaining concerns of CRISPR technologies highlight the question: ‘to what extent should a technology be used to eliminate undesirable traits?’ Who will be deciding the ethical use and removal of these traits? Although CRISPR technologies hold the potential to address global diseases that wreak havoc on the economies and welfare of populations, they also prompt concern for their future abuse and potential side effects. Overall, CRISPR presents a massive leap in the world of gene editing that has the potential to provide relief by addressing the symptoms of sickle-cell. Humanity is now entering into a new frontier of technology where survival is not just of the fittest, but left up to the powerful effects of technology.
References
1. Mayo Foundation for Medical Education and Research. (2022, March 9). Sickle cell anemia.
Mayo Clinic. Retrieved March 28, 2022, from
https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876
2. Stein, R. (2021, December 31). First sickle cell patient treated with CRISPR gene-editing still
thriving. NPR. Retrieved March 28, 2022, from https://www.npr.org/sections/health-shots/2021/12/31/1067400512/first-sickle-cell-patient-treated-with-crispr-gene-editing-still-thriving
3. Centers for Disease Control and Prevention. (2020, December 16). Data & statistics on Sickle
Cell Disease. Centers for Disease Control and Prevention. Retrieved March 28, 2022, from
https://www.cdc.gov/ncbddd/sicklecell/data.html
4. CRISPR/Cas9. CRISPR. (n.d.). CRISPR Therapeutics. Retrieved March 28, 2022, from
http://www.crisprtx.com/gene-editing/crispr-cas9
5. Stanford Medicine. (n.d.). CRISPR is a gene-editing tool that's revolutionary, though not
without risk. Stanford Medicine. Retrieved March 28, 2022, from
6. US Blood Supply Facts. Facts About Blood Supply In The U.S. | Red Cross Blood Services.
(n.d.). Retrieved March 28, 2022, from https://www.redcrossblood.org/donate-blood/how-to-donate/how-blood-donations-help/blood-needs-blood-supply.html
7. U.S. National Library of Medicine. (2022, March 1). What are the ethical issues surrounding
gene therapy?: Medlineplus Genetics. MedlinePlus. Retrieved March 28, 2022, from
https://medlineplus.gov/genetics/understanding/therapy/ethics/
8. Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos. Cell .
(2020,October29). Retrieved March 28, 2022, from
https://www.cell.com/cell/fulltext/S0092-8674(20)31389-1
9. Wu, K. J. (2020, October 31). CRISPR gene editing can cause unwanted changes in human
embryos, study finds. The New York Times. Retrieved March 28, 2022, from
https://www.nytimes.com/2020/10/31/health/crispr-genetics-embryos.html
10. Parichy, D. (2022, November). Reverse genetics. [Presentation]. University of Virginia, Charlottesville, VA, United States.