Is it ethical to genetically edit babies, or conduct trials that further science while neglecting participant consent? What crosses the line, and what is the line? These questions were just a few among those raised during our discussion of bioethics in Fred Hutch Pathways Explorers. I have always found discussions of morality and its application in real-world scenarios to be fascinating—thus, our introduction to ethical reasoning in science was notably impactful on me. First, we addressed the notion that ethics are not fully subjective. Instead, there are certain biomedical ethical principles that scientists are obliged to abide by. The first is respect for persons. By honoring the dignity and worth of each individual, protecting vulnerable populations, and obtaining informed consent from participants, medical professionals can ensure they are not violating the rights of those involved in their research. We also discussed the principle of beneficence, which obligates one to maximize benefits while minimizing harm. Although this seemed self-explanatory to me at first, I learned that there are countless scenarios in which the maximization of benefits comes with difficult consequences. For example, a study that furthers ground-breaking research in a particular field at the cost of quality of life for study participants likely wouldn’t adhere to this principle. Finally, we discussed the principle of justice through the 3Cs of Care, Community-Oriented, and Critical Perspectives. This principle emphasizes the prioritization of community relationships as well as dignity for disenfranchised populations. Furthermore, it stresses the confrontation of underlying systems that may have created inequities in treatment and elevates community concerns first and foremost. As we delved into examples of bioethics in real life, I was particularly affected by our discussion of the Tuskegee Syphilis Study. Beginning in 1932, this study recruited 600 Black men who were told they were being treated for ‘bad blood’, of which 399 were diagnosed with syphilis and 201 were used as a control group. In exchange for their participation, they were given free meals, medical exams, and other benefits. However, despite penicillin becoming a widely available treatment for syphilis, the medicine was deliberately withheld from study participants. With no treatment, participants suffered for thirty years until the study finally ended with a lawsuit, many of the patients having already passed. This study is a glaring example of bioethics violations with zero regard for informed consent or minimizing harm. I was especially interested in this study and in bioethics after learning more about the distrust of COVID vaccines by Black Americans in the present day. While at first, I was confused by the wariness surrounding the COVID vaccine, learning more about the racial bias and historical mistreatment of marginalized groups in medicine made me realize that those fears were valid. After discussing this topic with my fellow Explorers, we noted that what matters now is how the healthcare system moves forward to rebuild trust with disenfranchised communities and keep citizens fully informed on the safety and importance of getting vaccinated, while adhering to bioethical principles.
For the second portion of my blog post, I wanted to look into some of the ongoing cancer research taking place at Fred Hutch, specifically around immunotherapies. One that piqued my interest found that mRNA altering drugs could improve immunotherapies against cancer. In a study led by the Seattle Fred Hutchinson Cancer Research Center and the New York Memorial Sloan Kettering Cancer Center, scientists aimed to find drugs that could increase visibility of tumor cells, allowing a patient’s own immune system and checkpoint inhibitors to recognize and eliminate them. By using drugs that disrupt the mRNA process rather than the more dangerous option of damaging cellular DNA for the same end, the researchers were able to create tumor cells leading to the production of neoantigens on the cell surface, allowing the immune system to recognize the neoantigens as foreign and destroy the intended tumor cells in the process. Given how quickly mRNA degrades, altering mRNA instead of DNA allows scientists to avoid permanent mutations. In their study, they experimented with mRNA production disrupting drugs, specifically finding ones that briefly disrupt the spliceosome to produce cell-surface neoantigens and thus allow the immune system to identify the cells as foreign. For example, in an experiment in mice with Lewis lung carcinoma, giving the mice mRNA-disrupting drugs (specifically indisulam) significantly slowed tumor growth. Dr. Omar Abdel-Wahab and Dr. Robert Bradly, co-leads of the study, see the findings as promising for use alongside immunotherapy against cancer.
Figure from: Sydney X. Lu, et al, Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. Cell, Volume 184, Issue 15, 2021
https://doi.org/10.1016/j.cell.2021.05.038.
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