Ethics, Legal and Social Issues
UBC BIOMOD 2024’s project on the DNA Origami Box exemplifies the cutting-edge advancements within the field of nanotechnology and medical science. This innovative research not only holds promise for transforming treatment approaches but also brings to light critical ethical, legal, and social issues (ELSI) regarding informed consent, data protection, patient safety, and the ethical considerations surrounding experimental treatments.
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Doctor - Ethical usage of treatment for Prostate Cancer (PCa) using DNA box with limited research on long term effects.
The concerns in using a novel treatment technique stems from the unknown long term effects the treatment may have on the patient. Before the anti-CD3 antibody box can be used on patients to treat prostate cancer, there should be, ideally, longitudinal studies done on representative cohorts to investigate:
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Non-specificity of this drug: how the box may affect other cells in the body that express PSMA receptors on their surfaces.
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Effect of drug on cancer prognosis and potential relapse: T-cell and other immune-based therapy are known to alter genomic/epi;genomic signatures of prostate cancer which confers metastatic potential (Hirz et al., 2023).
Until more is known on the long term effects of the box on the body there will be reduced willingness for this treatment to be used by medical professionals.
Potential responses from non-researchers
Many medical professionals may be hesitant to use the treatment on their patients over other, more tested treatments (Medlinskiene et al., 2021). The early adoption of new drugs is based on many factors, one of which is the participation in clinical trials and the volume of prescribing (Lublóy, 2014). This may result in it not being adopted in medical settings where a patient may benefit from its use. It could prevent the treatment from being recognized as useful, resulting in limited use internationally.
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Patient - Informed Consent
Informed consent in clinical drug testing raises numerous challenges that must be addressed to ensure ethical and transparent research practices. One primary concern is that participants fully understand the study’s nature, benefits, and potential risks, which is critical for maintaining trust and integrity in the researcher-participant relationship. The Declaration of Helsinki provides a fundamental framework for addressing these concerns, emphasizing that participants must voluntarily consent after being adequately informed (Carlson et al., 2004). This includes a clear explanation of the study’s objectives, methods, potential risks, benefits, and alternative treatment options. In first-in-human research, ethical considerations become even more complex, as the study involves testing new drugs on humans for the first time, inherently carrying a higher degree of uncertainty and risk (Koonrungsesomboon et al., 2016). Researchers must ensure participants are fully aware of the experimental nature of the treatment and potential unknowns (Koonrungsesomboon et al., 2016). Additionally, researchers must address potential conflicts of interest to ensure that the information provided to participants is unbiased and comprehensive, maintaining the ethical integrity of the study. Overall, this project requires adherence to established ethical guidelines and a commitment to transparent and honest communication with participants.
Potential responses from non-researchers
A lack of rigorous informed consent processes and inconsistent data protection practices could lead to mistrust among patients and reluctance from ethics committees and hospital administrators to support the new DNA Origami Box treatment. This mistrust may result in reduced patient participation in clinical trials, potentially limiting the collection of vital data and slowing down the development of the treatment. Additionally, concerns about the security of sensitive patient information might cause medical practitioners to hesitate in administering the treatment, fearing legal repercussions and breaches of patient confidentiality. Furthermore, an ethical dilemma arises if the project’s drug proves to be ineffective, as patients receiving it may potentially experience worse outcomes compared to the control group, which typically receives a gold standard treatment known to be somewhat effective. This potential for patient harm underscores the importance of robust ethical considerations and transparency in the informed consent process.
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Patient - Costs associated with receiving this novel therapy
Although our proposed therapy is designed to be lower cost compared to existing T cell therapies such as CAR T cells, the costs associated with the research, development, testing and deployment of a novel therapy can quickly accumulate. As such, it may not be accessible to lower income individuals or those without a comprehensive insurance plan. This unequal access can further expand to a global scale in which developing countries may not be able to afford, and therefore have access, to this therapy compared to developed countries. Additionally, these high costs can exacerbate existing healthcare inequities in marginalized communities such as racial and ethnic minorities as these communities often already face barriers when accessing existing and new treatments (Bourgeois et al., 2023).
Potential responses from non-researchers
To ensure the drug is accessible to all socioeconomic barriers, politicians and federal committees will likely intensify existing efforts and devise new strategies to ensure equitable distribution. This may include implementing subsidies and grants, expanding insurance coverage, and fostering new partnerships or agreements between governments, pharmaceutical companies and manufacturers.
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Patient - Can patients be harmed by not receiving the standard of care?
Administering the best treatment available to patients is crucial. When this therapeutic reaches the clinical trial phase, patients may be randomly assigned to receive the new therapeutic, current standard of care treatment or a placebo treatment. Depending on the safety and efficacy of the therapeutic, patients may feel that they are being deprived of receiving the best care if it performs poorly and the standard of care has shown to be effective or resentful if they are not receiving the therapeutic and it is more effective than the standard treatment of care. There are risks and benefits that patients must be aware of before participating in the trial.
Potential responses from non-researchers As DNA origami is a relatively new technology, the therapeutic might be faced with backlash and skepticism.
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Researchers - Environmental and health impacts of waste products
Research facilities investigating or manufacturing our new therapeutic solution to prostate cancer may have concerns about the impact of waste products on the health and well-being of staff working on the project and possible negative effects on the environment. As a result, all waste and byproducts synthesized during the development of our project should be monitored for potential health hazards on researchers working with the box and harmful effects on the environment during disposal. For instance, to test the efficacy of our therapeutic on T-cell recruitment, T-cell media containing Trypsin and EDTA is required, both of which are known irritants that require careful handling and proper protective equipment to minimize injury to the eyes and respiratory system if inhaled (SAFETY DATA SHEET Ethylenediaminetetraacetic Acid, n.d.; SAFETY DATA SHEET Trypsin, n.d.). Moreover, our experiments to test T-cell recruitment employ CXCL16 chemokines as a positive control chemoattractant, which requires special disposal of waste and excess products through either a licensed disposal facility or incineration (SAFETY DATA SHEET CXCL16, from Mouse, n.d.). We have already taken steps to reduce safety hazards to protect researchers involved in the project by substituting more harmful chemicals, such as ethidium bromide, for safer alternatives with less impact on the environment, like SYBR Safe DNA stain for gel electrophoresis, in our procedures. Compliance and collaboration with regulatory organizations deciding on appropriate hazardous waste management would also be required to ensure proper disposal of all materials used and produced for our project and to ensure the safety of all personnel. An example of this is the handling and disposal of prostate cancer cell lines to test our project, as chemical suppliers recommend disposing of contaminated objects and waste following legislative requirements (Cell Culture Fundamentals, n.d.), and improper handling and insufficient safety measures can pose health risks such as the transferring of cancer cells to workers (Geraghty et al., 2014).
Potential responses from non-researchers
Ensuring proper disposal of waste products to mitigate impacts on the environment is critical as improper disposal or serious negative side effects may raise ethical concerns from research facilities and the public. Research facilities may be hesitant to be involved in our project, and the public may be reluctant to use the therapy. As well, negative effects on the environment could result in opposition from the public who are concerned about the environment and public safety. As such, ensuring proper care is taken in waste disposal and compliance with regulatory agencies can build confidence from the public.
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Researchers - Ethical implications of material sources and DNA origami manufacturing
The use of human or animal-derived material raises significant ethical issues. For human cells or tissue used, informed consent from donors is vital.The manipulation of DNA raises concerns about the potential misuse of genetic information. It is important to consider how to safeguard the privacy of genetic data used in the development and application of the DNA origami box. Additionally, unauthorized access could lead to genetic discrimination or other forms of harm
Potential responses from non-researchers
Patients may express reluctance to participate in the therapy due to fears of genetic data misuse. Ethical review boards and regulatory agencies might require rigorous privacy protection measures as a condition for approving the therapy.
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Manufacturing Companies - Regulatory Compliance
Regulatory compliance is integral to the development of a novel immunotherapy. The FDA, EMA, PMDA, and other such regulatory bodies put forth regulations to ensure patient safety and drug quality. FDA investigators reinforce this by visiting a facility and determining whether it is adequately controlling its manufacturing operations. This includes having strong quality management systems and robust operating procedures in place, the use of appropriate quality raw materials, detecting and investigating product quality deviations and maintaining reliable testing laboratories (Commissioner, 2022). Approval from these organizations is a prerequisite for market access, allowing the manufacturer of the drug to make it available to patients who are most in need of it. Acquiring approval can be a lengthy process due to an organization’s stringent requirements and complex regulations, as well as the cost of compliance. Drug discovery can take over 10-15 years and cost anywhere from thousands to billions of dollars, from preclinical testing to clinical trials and finally application and review. Nine out of ten drug candidates fail during clinical trials and drug approval after entering clinical studies (Smoteks, 2024; Sun et al., 2022). This can be a barrier to researchers as a great deal of time and money must be put into ensuring all aspects of a new drug meet these standards, which is potentially delaying a life-saving treatment. Non-compliance can result in severe legal and financial consequences. Novartis had made efforts in repurposing an anti-inflammatory drug called canakinumab in cancer, but the drug failed its third phase 3 trial and in 2018 failed to get expanded approval from the FDA. This resulted in a loss of $2 billion in potential revenue (Post et al., 2022).
Potential aspects of this project that could be scrutinized in the approval process include the introduction of foreign DNA into the human body and target specificity. If not carefully designed and tested, these aspects could cause harm to a potential patient and result in failed FDA approval.
Potential responses from non-researchers
In the case of a potentially life-saving drug, patients and advocacy groups may demand for expedited access to the drug. This could involve petitioning regulatory agencies to prioritize the review of such a drug. In addition, they may advocate for increased transparency in the drug review process, as well as for more information on clinical trials.
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Stakeholders - Intellectual Property
Because the project uses ideas and tools from a variety of different sources, in the case that it is commercialized for broader use, there are concerns over whether any intellectual property rights will be violated. Intellectual property exists to ensure that creators are properly credited for their work, and that individuals cannot profit off of others’ work. In order to ensure that we don’t run into legal issues when selling/re-producing our work, and to make sure we are giving credit to the right people, we must make sure that the property rights of all aspects of the project are respected.
When applying for patenting intellectual property, it is important to consider whether our DNA origami design for cancer immunotherapy is similar to a previously approved design. Furthermore, although there usually aren’t many issues with the use of open-source softwares such as Swiss and caDNAno, we should make sure to credit all programs that contributed to the final design.
Potential responses from non-researchers
If the proper measures to respect intellectual property rights are not taken, then we could face legal repercussions, and ethical backlash from stakeholders, clients, and the general public. Other companies and research facilities may become reluctant to work with or support us if we are unable to respect and credit others for their work.