Ethical Evaluation of CAR_Ma Using Rule Utilitarianism and the Capability Approach
(This framework was developed under the guidance of HKU’s and Hong Kong Ethics Lab’s Dr. Brian Wong.)
Introduction
The CAR_Ma project utilizes advanced gene-editing technologies, including CRISPR/Cas9 and self-replicating RNA (srRNA), to offer a more effective treatment for solid tumors such as hepatocellular carcinoma (HCC) and small-cell lung cancer (SCLC). While CAR_Ma introduces considerable innovations in cancer treatment, it also raises significant ethical considerations. This evaluation assesses these ethical challenges through the frameworks of Rule Utilitarianism and the Capability Approach.
Rule Utilitarianism argues that the rules governing actions should maximize societal utility while minimizing harm when applied universally (Nathanson, n.d.). This perspective is geared towards ensuring the greatest benefit for the largest number of people. Conversely, the Capability Approach, introduced by Amartya Sen and Martha Nussbaum, focuses on enhancing individual freedoms and capabilities, particularly in the areas of health, autonomy, and dignity (Robeyns & Byskov, 2020). By combining these two ethical frameworks, the analysis of CAR_Ma shifts beyond happiness or pleasure to focus on creating real opportunities for individuals to thrive—specifically regarding health, security, and autonomy.
Unified Rule Utilitarianism and the Capability Approach in CAR_Ma
When applied together, Rule Utilitarianism and the Capability Approach offer a robust framework to evaluate CAR_Ma's ethical foundation. Rule Utilitarianism considers the societal benefits of the therapy, while the Capability Approach highlights the individual experience, particularly in terms of how CAR_Ma improves personal health, autonomy, and dignity. Both frameworks converge on core ethical objectives: ensuring patient safety, promoting equitable access to healthcare, and minimizing harm typically associated with cancer treatments.
Managing Risks and Enhancing Safety
CAR_Ma incorporates several layers of safety measures, which align with both ethical frameworks by minimizing risks and protecting patients. The use of gene-editing technologies like CRISPR/Cas9 brings inherent risks, such as unintended mutations, off-target effects, and the uncontrolled replication of genetically modified cells. These risks necessitate stringent safety protocols.
One key safety mechanism in CAR_Ma is the TMP kill switch, which allows for the controlled halting of RNA self-replication and the expression of therapeutic systems like CAR in response to trimethoprim (TMP). This safeguard ensures the therapy remains manageable and prevents unintended effects from escalating, addressing safety concerns directly.
Furthermore, plasmid sequencing provides continuous monitoring, tracking potential genetic mutations during treatment. This feature enables early detection of harmful changes, maintaining therapeutic efficacy while reducing risks. These safety measures align with Rule Utilitarianism by providing scalable safety protocols that can be applied to larger populations, thus reducing societal risks. The Capability Approach supports these safeguards by promoting patient security, ensuring that individuals can undergo the therapy without fear of unsafe side effects.
Referring to McGill's report on ethics in synthetic biology, these safety mechanisms are fundamental to ensuring ethical practices (McGill iGEM, 2023). Biosafety and biocontainment measures are necessary to avoid unintentional harm to both patients and the environment. By incorporating systems like the TMP kill switch and plasmid sequencing, CAR_Ma upholds broader bioethical principles, safeguarding both public health and environmental integrity.
Promoting Transparency and Accountability
Transparency stands as a central ethical pillar of CAR_Ma, CAR_Ma promotes open science by making its research data, lab notebooks, methods, primers, and genetic sequences publicly available on our wiki pages. This emphasis on transparency serves multiple ethical functions. It fosters accountability by enabling external researchers and future teams to verify and replicate findings, and it builds trust among patients and the public, allowing them to make informed decisions regarding the therapy.
Collaboration with external researchers, from a Rule Utilitarian view, maximizes societal utility. When research findings are shared openly, other researchers can build upon the data, leading to advancements that benefit society at large. McGill's report on scientific integrity highlights the importance of transparency in maintaining ethical standards, noting that openness facilitates external scrutiny, which reduces the risk of errors, bias, or fraud and enables us to form a functional framework to evaluate our project (McGill iGEM, 2023).
For the Capability Approach, transparency helps expand patient autonomy. When patients have access to relevant information—including risks, side effects, and potential benefits—they can make decisions aligned with their values and long-term health goals. CAR_Ma aims at enhancing individual freedoms and equipping people with the necessary resources to lead fulfilling lives. Furthermore, transparency in CAR_Ma resonates with the common principles of clinical ethics, which emphasize that a lack of transparency can undermine trust between patients and healthcare providers. By ensuring that all aspects of the project are accessible and open, CAR_Ma upholds a high ethical standard. In the event of unforeseen side effects or complications, transparency ensures the broader scientific community and the public are promptly informed and can respond accordingly.
Addressing Social Implications and Promoting Accessibility
CAR_Ma’s most significant ethical contribution lies in its potential to address healthcare disparities by expanding access to advanced cancer treatments. In a world where healthcare inequities often prevent low-income populations from accessing cutting-edge medical technologies, CAR_Ma’s design prioritizes scalability, affordability, and ease of distribution, making it a viable option for patients across various socioeconomic settings. By targeting the tumor microenvironment (TME), CAR_Ma’s therapeutic reach extends to a broad range of solid tumors, increasing its overall impact.
The use of nanostructured lipid carriers (NLCs) allows the therapy to be stored at room temperature, significantly lowering logistical costs and making the treatment more accessible to remote and underserved regions with limited cold-chain infrastructure. CAR_Ma’s in vivo injection method and self-replicating RNA design further enhance accessibility by simplifying administration, eliminating the need for frequent hospital visits or advanced technical expertise. This reduces the strain on healthcare systems and makes the therapy more accessible to low-income populations.
CAR_Ma can help make life-saving treatments available to a larger population. By making advanced cancer treatments more affordable and accessible, CAR_Ma empowers people in low-income areas to access the care they need, promoting autonomy and well-being across socioeconomic divides.
Enhancing Health Capabilities and Societal Good
Compared to therapies like CAR-T, which struggle with treating solid tumors, CAR_Ma offers a more scalable and effective alternative. By enhancing the capabilities of modified macrophages to target cancer cells, CAR_Ma improves both survival rates and quality of life for cancer patients, which maximizes positive health outcomes for a broader population.
CAR_Ma also alleviates many of the financial and logistical challenges traditionally associated with cancer treatment. Chemotherapy, for instance, is often expensive, comes with severe side effects, and requires frequent hospital visits. In contrast, CAR_Ma’s more targeted delivery system, reduced toxicity, and simplified administration make it a more accessible option for both patients and healthcare providers. This aligns with the Capability Approach, as it enhances individual health capabilities and promotes autonomy by offering a more efficient and less burdensome treatment option.
Conclusion
By integrating Rule Utilitarianism and the Capability Approach, this ethical evaluation demonstrates that CAR_Ma represents a significant ethical advancement in cancer therapy. The project improves patient outcomes while maximizing societal utility by addressing healthcare inequities and fostering transparency. Safeguards like the TMP kill switch and plasmid sequencing enhance both safety and patient autonomy, ensuring CAR_Ma adheres to high ethical standards. Furthermore, CAR_Ma sets a precedent for future synthetic biology projects, emphasizing the importance of safety, transparency, and accessibility in medical innovation.
References
McGill iGEM. (2023). Bioethics. Proteus. https://2023.igem.wiki/mcgill/bioethics/
Nathanson, S. (n.d.). Act and Rule Utilitarianism. Internet Encyclopedia of Philosophy. https://iep.utm.edu/util-a-r/
Robeyns, I., & Byskov, M. F. (2020, December 10). The Capability Approach. Stanford Encyclopedia of Philosophy. https://plato.stanford.edu/entries/capability-approach/