By Katelyn Crawford
Published 8:50 EST, Mon October 25th, 2021
The CRISPR/Cas9 technology is continually advancing and improving with rigorous scientific testing. This technology leads the scientific community closer to finding cures for genetic diseases, but it also creates more questions and ethical concerns. CRISPR technology is one method of genetic engineering that cuts out and replaces or repairs specific segments of DNA sequences, including sequences that code for specific monogenic diseases. This emerging technology holds many potential lifesaving benefits but fails to address long-standing societal concerns about the dangers of genetic engineering.
The CRISPR technology is expected to cure many single-gene diseases such as Sickle Cell Anemia or Cystic Fibrosis. For example, CRISPR could be used to alter the gene responsible for Cystic Fibrosis, called the CFTR gene; this technology would correct known mutations that give rise to Cystic Fibrosis. However, thousands of different mutations could cause the disease, and not all of these mutations can be targeted with our current technologies. Therefore, genetic sequencing would need to be performed on each patient to identify which cases could be cured with gene therapy and which are currently genetically inaccessible. Due to CRISPR making permanent changes to the genetic code, much research must be performed before the technology can be approved for testing on human patients with specific CF-related point mutations. Furthermore, in 2018 a new version called base editing was created, which was able to fix some CF mutations without cutting the DNA sequence. The original CRISPR technology would cut the DNA strand, potentially harming the person by damaging the DNA sequence with inappropriate DNA repair; instead, this new technology directly repairs the mutation site without cutting the DNA sequence . This base editing technology is a safer way to use CRISPR to edit gene sequences to treat Cystic Fibrosis and eventually many other diseases.
One crucial aspect of successful treatment is identifying this new CRISPR enzyme to target the correct cell types within specific organs. This is important because genes often play critical roles in developing or functioning multiple cell types or organs. A mutation may be harmful to heart function but benign or helpful to brain function. One example of this dichotomy is the intended targeting of survival genes in cancer cells that unintentionally harm the immune cells responsible for clearing the cancer cells; this unintentional harm then decreases the treatment efficacy. So while these advancements to the CRISPR technology are beneficial to patients and will revolutionize the treatments of some diseases, a lot is still unknown. One area of active research focuses on the removal of white blood cells from a patient, followed by gene editing and then inserting the edited cells back into the affected patient. Scientists believe this approach could be used to treat certain kinds of cancer and infectious diseases, like HIV. It combines CRISPR technology with the technology to insert the CRISPR raw materials into a cell . Scientists now argue that they can use electrical fields instead of viruses to introduce gene-editing materials into immune cells to treat various cancers. These newly edited immune cells then are inserted back into the body, where the cells find and attack the tumor. Many questions must be answered before it can be approved for human use. For instance, how long would it take for the modified cells to find and destroy the tumor? Will these cells show autoimmune behavior and also destroy healthy tissue? The technology should allow for the quicker treatment of diseases like HIV and Cancer, where weeks to months make a significant difference for patient survival.
Since all of the changes made to the genome sequence by CRISPR are permanent, it is important to note that the technology is only being considered for use in somatic cells. These are cells in the body that do not get passed down to any children. There is concern that CRISPR use in germline cells may permanently adjust the genes in humans passed down to children, including any mistakes that the editing technology may have made. This brings up the idea of how technology would change genetic diversity. The prevention or treatment of life-threatening diseases is helpful technology, but beyond unintentional mistakes getting introduced into the gene pool, where does the editing stop? Is there any way for people to prevent the use of CRISPR for editing medically insignificant traits, such as eye color? Due to these concerns, the scientific community is attempting to hold off on all genetic engineering of embryos to allow time for ethicists and the law to catch up with scientific progress. Clear guidelines will need to be provided before using these technologies. There is limited funding for research available, so studying CRISPR to treat life-altering diseases takes top priority; introducing the possibility of researching medically insignificant mutations would waste resources better served to prevent or correct life-threatening conditions. People’s lives could depend on this treatment, and many ethical issues arise as a result.
Pending future approval of CRISPR for medical cures, another significant drawback is the cost. This technology is new and very expensive. Researching and repairing one protein could cost millions of dollars, including the cost of many stages of trials needed for FDA approval, animal care for testing, the cost of patents, and licensing to a company. Paying the researchers and other employees leads to a significantly higher price, which is prohibitive to many families. Additionally, the time to conduct the necessary research before use in patients may nullify the need for treatment if the process takes too long or cannot be scaled up effectively. Thus, the costs associated with CRISPR are not accessible to most families, which raises the question “If only some patients can afford treatment with CRISPR, what makes these people more qualified or deserving of treatment?”. To illustrate this point, in 2019, Novartis released a gene therapy called Zolgensma to treat Spinal Muscular Atrophy. In the base-case analysis, the company’s subjective value was estimated at $900,000 per treatment . This is the cost of a single treatment, but it is hard to determine how many treatments a single patient will need with the unknowns of gene therapy. As a result, only 700 patients were approved for the treatment. In the future, where CRISPR has received approval for a broader range of genetic diseases, it will not be cheap at its current scale, and therefore many people will not be able to afford it. As the technology changes and is streamlined, cost-effectiveness may also improve, but if the costs fail to decrease, what are the determining factors in who will get this life-saving treatment? CRISPR is controversial, costly, and time-consuming to bring from start to finish; with CRISPR’s potential to yield so many treatments weighed against its considerable drawbacks, how can the overall impact of CRISPR truly be determined? And will CRISPR turn out to be the silver bullet of gene therapy, or will it fall short of expectations?
Katelyn Crawford, Youth Medical Journal 2021
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