By Asia Lie
Curing cancer is the dream accomplishment for an immense number of researchers and scientists in the world today. Research funding in cancer for the National Cancer Institute in the USA is estimated to be a total of $6.4 billion for 2020.1 This has grown substantially from about $500 million in 1972 to $6.5 billion in 2021.2 As interest and activity in the search for a cure for cancer grows, it is important to reflect on the ethical implications of this goal.
Cancer is a result of mutations in DNA.3 Normally, the cell is able to avoid mistakes in the DNA through pathways and checks made to either fix the mistake or abort the cell entirely.3 In cancer, DNA mutations build up, allowing cells to bypass the important systems in place to prevent mutations.4 One such system is apoptosis, programmed cell death. Apoptosis often occurs when a cell’s DNA has built up several mutations over time and is a natural process in the body.5To sum up, cancer is made of our own cells that have mutated to prevent their own death, replicating without control and amassing tumors. There are several pathways and genes that mutations occur in, which allow for the growth of tumors.
When a cell is able to avoid the “checks and balances” that it has enacted, it becomes a cancer cell. The mutations that begin this rebellious behavior can arise over time naturally due to age, exposure to sunlight, mistakes in the DNA replication process, and many other factors.6 They can also arise due to exposure to certain toxic substances.6 A tragic example of this is the firefighters present at the 9/11 attacks on the World Trade Center, who were exposed to large amount of carcinogens at the scene and now experience a higher risk of cancers including prostate and thyroid cancers.7This article focuses on the cancers that arise with age due to accumulated mutations over time.
Investigators are targeting the mutations that occur in important cell regulating pathways as a treatment for cancer. Some of the most mutated genes in cancer include, KRAS, PIK3CA, BRAF, and TP53.8 TP53 is the most commonly mutated gene, mutated in about 35% of all cancers.8 This gene encodes the p53 protein which plays an important role in cell cycle regulation, allowing the cell to check and fix mistakes in DNA replication and activating apoptosis if significant DNA damage has occurred.9 In cancers, a mutation of TP53 causes a loss of function in p53, affecting the pathways that p53 is normally involved in.10 By targeting and attempting to fix any mutations in this gene, researchers believe that the restoration of the important functions listed above would help treat cancers.
As mentioned above, to treat cancers that arose through accumulated mutation, many researchers are looking at reversing the effects mutations have on important pathways, especially pathways involving cell cycle regulation. The pathways involving mutated p53 are a popular target. There are a number of studies attempting to restore these pathways. As of now, these involve either promoting the “normal” state of p53 or suppressing the mutated state of p53 to re-establish p53’s normal function.10 These kinds of treatments can keep the effects of a mutation at bay; however, they can’t cure the cancer.
To avoid even developing cancers or to cure them completely, researchers can look towards the mutations themselves: how to reverse them. In other words, going straight to the source instead of treating the symptoms of a mutation. Theoretically, this involves perfecting our DNA to remain without mutations: making it immortal. This cure will likely involve using CRISPR technology and gene editing techniques to reverse the mutations found in a cancer cell line.11While we are far from a sufficient therapy using this method, it could become more commonplace as gene editing techniques improve. If we pursue this kind of treatment, what are other implications of making our DNA immortal? Could this technology be used to reverse or stop the symptoms of aging? Would it extend our lifetime significantly? What are the ethical implications of making our cells theoretically immortal?
Cancer is mainly a disease of the elderly, except mainly the cases of pediatric cancers. As of now, heart and circulatory disease causes the most death in the elderly population.12 As improvements in medicine overcome this cause of death, cancer will likely be the next significant obstacle to an increased human lifetime. This is one ethical implication that accompanies most medicine in general: increased lifetime. More unique ethical consequences arise with the immortalization of DNA and gene editing in general.13 Could our cells, and therefore our bodies, become immortal? How would this affect population size and the carrying capacity of our planet? While there is no way as of now to know the consequences of immortalizing DNA, we could be affected by ethics involved in increased lifetime, slowed aging, modifications to the natural body system, and more.
Barring some cases of cancer, the cure we are searching for may have a variety of ethical implications revolving around the search to make our DNA immortal, perfect, or without possibility of a mistake that could lead to cancer. While the cures of most diseases and disorders can be intertwined with complex ethical problems, the cure to cancer marks an important transition from improving quality of life to extending life indefinitely. Will this be a quest for the fountain of youth or will the war on cancer succeed with a different strategy?
References:
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11. Abuhamad AY, Mohamad Zamberi NN, Sheen L, Naes SM, Mohd Yusuf SNH, Ahmad Tajudin A, et al. Reverting TP53 Mutation in Breast Cancer Cells: Prime Editing Workflow and Technical Considerations. Cells [Internet]. 2022 May 11 [cited 2023 Jan 21];11(10):1612. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139850/
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13. National Human Genome Research Institute. What are the ethical concerns of genome editing? [Internet]. National Human Genome Research Institute. 2017. Available from: https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns
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