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ELSI (Ethical, Legal and Social Issues)

Introduction

Research on artificial biomolecular devices represents a groundbreaking field in nanotechnology, with the potential to revolutionize various applications, including drug delivery, targeted therapies, and nanoscale manufacturing. While the scientific and technological advancements in biomolecular engineering are remarkable, they also raise significant ethical, legal, and social implications (ELSI). This analysis delves into the ELSI associated with these types of research, specifically regarding Team Sendai’s project in BIOMOD 2023, covering aspects such as informed consent, privacy concerns, intellectual property issues, safety considerations, and societal implications. It aims to shed light on the multifaceted ELSI challenges and opportunities that researchers, policymakers, and society at large should consider as this innovative technology continues to evolve.


Informed Consent

Informed consent is a foundational principle in biomedical research, ensuring that participants are fully aware of the risks and benefits associated with their involvement.

    1.1 Human Subjects Research:

  • Our research did not involve any human subjects. As such, no informed consent was required nor gathered

    • 1.2 Data Privacy:

  • The data that we present on our project page and presentation, is free of any uncited and unpermitted data, published or unpublished, that may concern the privacy of someone or their work.

Privacy Concerns

Privacy concerns are a critical ELSI issue in DNA-related research, particularly regarding the storage, analysis, and sharing of genetic information. These concerns can be broken down into several subcategories:

    2.1 Genetic Information, Discrimination, and Familial Privacy:

  • Because our DNA origami uses completely synthetic staple DNA strands ordered from Eurofins Genomics, no genetic information is included in any of our materials, disabling any information leak regarding genetic materials.

    • 2.2 Virus DNA

  • We employed the p8064 sequence to use as our scaffold, which is a single stranded origami vector that was based on a part of the M13 bacteriophage’s genetic material. The guidelines on animal experiments by the International Guiding Principles for Biomedical Research, published by the Council for International Organizations of Medical Sciences (CIOMS), have no regulations concerning phage and other viruses.

Safety Considerations

DNA origami research also raises safety concerns that encompass both physical and environmental aspects.

    3.1 Biosecurity:

  • The ability to engineer DNA structures has implications for biosecurity, as it could be misused for harmful purposes such as DNA-based sequestration of important biologically active molecules and harmful DNAzymes, among others.
  • Responsible research and safety protocols, which were determined by a central council, should be in place to prevent misuse and secure materials used in DNA origami research.
  • In our project, the use of a soap bubble membrane became one of the highlights. In doing so, we had to use amphiphilic molecules in a higher concentration than what is generally used of those reagents in traditional molecular biology experiments. As such, we have decided to treat such solutions as potentially dangerous solutions and disposed of them in a controlled manner as per the university’s regulations.
  • In our project, the use of SYBR Gold was very frequent. As SYBR Gold intercalates to DNA and is liable to cause cancer, every use and disposal of SYBR Gold-containing solutions were strictly documented and performed as per the university’s regulations.

    • 3.2 Environmental Impact:

  • The production and disposal of DNA origami materials may have environmental consequences such as the unintentional introduction of new evolvable genetic information to the environment. As such, we have made sure that all DNA-based materials are disposed of in accordance with the university’s regulations.
  • In our experiments, many plastic-based equipment and disposables were used and therefore are a liability to the environment as they may turn into microplastics and damage many forms of wildlife. Researchers should consider the environmental footprint of their work and develop sustainable practices, such as ensuring that processed plastic waste is sent to the appropriate recycling facility.

Legal Due Diligence

    4.1 Handling of Nucleic Acids

  • Various international regulations on the use of DNA and RNA have been defined, including the Convention on Biological Diversity, the Cartagena Act, etc. Currently, such regulations in Japan are still being developed, although any handling of DNA as a carrier of genetic information is strictly regulated. However, handling of these molecules as materials used in artificial molecular systems is not yet defined anywhere in the world, causing the management to be handled by the person in charge after some review by a central authority.

    • 4.2 Clinical Trials and Medical Applications

  • One of the main applications of many molecular robotics research is medical. In this case, the referencing of established rules regarding the development and clinical trials of other molecularly engineered drugs such as engineered monoclonal antibodies is needed. It is necessary to undergo clinical trials based on the existing ethical guidelines, while also complying with the outline of Good Clinical Practice (GCP).

    • 4.3 Biological Weapons

  • The Biological and Toxin Weapons Convention (BTWC), or the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction, which was employed from 1975, is functioning as the central regulations in prohibiting biological weapons.
  • Although artificial DNA devices may not function in itself as a weapon, there is a possibility of unsupervised modifications. In this case, since there is a high possibility that the products may not fall under the jurisdiction of weapons or toxins as defined in previously established guidelines, there is a need to construct a firm law surrounding this topic.

Intellectual Property Issues

Intellectual property (IP) issues are central to the ELSI of any research, especially in novel fields such as nanotechnology, as the technology is often patented. Patents can both facilitate and hinder research, and they raise questions about accessibility, innovation, and equitable benefits.

    5.1 Patenting DNA Origami Techniques:

  • The patenting of DNA origami techniques can foster innovation by providing incentives for research and development.
  • However, patent exclusivity can limit access to the technology and potentially hinder its broad application in research and industry.

    • 5.2 Licensing and Access:

  • The licensing of patented DNA origami techniques must be structured to ensure fair access and reasonable fees, especially in the context of academic research and resource-limited settings.
  • Overly restrictive licensing can stifle scientific progress and limit the technology’s potential benefits.

    • 5.3 Use of Technology

  • We herein state that no inaccessible patented technology was used in our project and no violation of any patent right was committed.
  • We also made use of publicly available softwares such as caDNAno, CanDo, oxDNA, NUPACK, among others.

Societal Implications

The societal implications of DNA origami research extend to cultural, economic, and ethical domains. Efforts to engage the public in ethical discussions, establish rigorous regulatory frameworks, and promote transparency can help mitigate these concerns. The responsible use of artificial biomolecular devices is critical to harness its potential for the betterment of society while addressing the apprehensions and criticisms that have emerged. Balancing innovation and ethics is a challenging but necessary task in navigating the complex terrain of the topic.

    6.1 Cultural and Ethical Values:

  • DNA origami research may challenge cultural and ethical beliefs, particularly regarding genetic engineering.
  • Ethical considerations include the moral boundaries of manipulating DNA and the potential for designer organisms or materials.

    • 6.2 Economic Disparities:

  • The economic implications of DNA origami research relate to the disparities in access to and benefits from the technology.
  • Concerns about exacerbating existing social and economic inequalities should be addressed.

    • 6.3 Research Priorities:

  • Society should play a role in setting research priorities in DNA origami to ensure that research efforts align with societal needs and values.
  • Public engagement and transparent decision-making can help balance scientific innovation with ethical considerations.

    • 6.4 Societal Impact

  • One of the most transformative areas of biomolecular engineering is the development of new medical therapies. The manipulation of biological systems at the molecular level has enabled the creation of custom-made drugs, vaccines, and therapies. Targeted treatments for cancer, genetic disorders, and infectious diseases are becoming increasingly precise, reducing side effects and improving patient outcomes.
  • Aside from medical applications, these technologies may contribute to the development of advanced bioenergy technologies, such as algae-based biofuels and synthetic photosynthesis, which harness the power of sunlight to produce clean energy.
  • However, the potential to create new life forms or modify existing ones has generated fear of the unknown. The unpredictable consequences of manipulating biological systems at the molecular level raise concerns about unintended and irreversible changes to the natural world. Critics argue that we should exercise caution and restraint in the pursuit of such transformative technologies.

Conclusion

Artificial biomolecular device research is a groundbreaking field with vast potential for various applications. However, its progress raises a complex array of ethical, legal, and social implications that necessitate careful consideration. Informed consent, privacy concerns, intellectual property issues, safety considerations, and societal implications are all intertwined with the development of this technology. Addressing these ELSI challenges requires collaborative efforts between researchers, policymakers, and the broader society to ensure that such a transformative research field proceeds responsibly, ethically, and equitably. As the field continues to evolve, ongoing dialogues and ethical guidance will be essential in navigating the ELSI landscape of DNA origami research.

Reference

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