ELSI (Ethical, Legal and Social Issues)

ELSI
(Ethical, Legal and Social Issues)

ELSI

(Ethical, Legal and Social Issues)

Introduction

Introduction

In the pursuit of advancing human space exploration, one of the most pressing health challenges is the weakened immune response experienced by astronauts in microgravity environments. Our project addresses this issue through the development of a DNA origami-based nanostructure specifically engineered to dynamically modulate immune responses. DNA origami, a technique that folds DNA strands into precisely defined nanoscale shapes, serves as the foundation of our design. Drawing inspiration from the Hoberman sphere’s expandable structure, our therapeutic device is designed to transition between open and closed configurations in response to specific stimuli, such as radiation or chemical signals. This transition alters the positioning of CpG oligonucleotides—short DNA sequences known to stimulate immune activity—attached to the device. By adjusting the spacing of these CpG sequences, the nanodevice aims to regulate immune function with precision as it travels through the bloodstream. Our goal is to create an innovative platform that not only advances biomedical engineering but also enhances our understanding of immune regulation, contributing to safer and healthier space missions.

In the pursuit of advancing human space exploration, one of the most pressing health challenges is the weakened immune response experienced by astronauts in microgravity environments. Our project addresses this issue through the development of a DNA origami-based nanostructure specifically engineered to dynamically modulate immune responses. DNA origami, a technique that folds DNA strands into precisely defined nanoscale shapes, serves as the foundation of our design. Drawing inspiration from the Hoberman sphere’s expandable structure, our therapeutic device is designed to transition between open and closed configurations in response to specific stimuli, such as radiation or chemical signals. This transition alters the positioning of CpG oligonucleotides—short DNA sequences known to stimulate immune activity—attached to the device. By adjusting the spacing of these CpG sequences, the nanodevice aims to regulate immune function with precision as it travels through the bloodstream. Our goal is to create an innovative platform that not only advances biomedical engineering but also enhances our understanding of immune regulation, contributing to safer and healthier space missions.

Informed Consent

Informed Consent

1.1 Human Subjects Research

Our research did not involve human participants, and therefore, no informed consent was required or obtained.

1.2 Data Privacy

All data presented on our project page and in our presentation is entirely original and does not include any uncited or unapproved data, whether published or unpublished, that might infringe upon someone’s privacy or intellectual property.

1.1 Human Subjects Research

Our research did not involve human participants, and therefore, no informed consent was required or obtained.

1.2 Data Privacy

All data presented on our project page and in our presentation is entirely original and does not include any uncited or unapproved data, whether published or unpublished, that might infringe upon someone’s privacy or intellectual property.

Privacy Concerns

Privacy Concerns

2.1 Genetic Information, Discrimination, and Familial Privacy

Our DNA origami design relies exclusively on synthetic staple DNA strands sourced from Integrated DNA Technologies, ensuring that no genetic information from living organisms is incorporated into our materials. This eliminates any potential for genetic information leakage and addresses privacy concerns related to DNA data.

2.2 Viral DNA

For our scaffold, we utilised the p7429 sequence, a single-stranded origami vector derived from a portion of the M13 bacteriophage genome. According to the International Guiding Principles for Biomedical Research (CIOMS), which provides guidelines on animal experiments, there are no specific regulations regarding the use of phage or similar viruses, further validating our choice of scaffold.

2.1 Genetic Information, Discrimination, and Familial Privacy

Our DNA origami design relies exclusively on synthetic staple DNA strands sourced from Integrated DNA Technologies, ensuring that no genetic information from living organisms is incorporated into our materials. This eliminates any potential for genetic information leakage and addresses privacy concerns related to DNA data.

2.2 Viral DNA

For our scaffold, we utilised the p7429 sequence, a single-stranded origami vector derived from a portion of the M13 bacteriophage genome. According to the International Guiding Principles for Biomedical Research (CIOMS), which provides guidelines on animal experiments, there are no specific regulations regarding the use of phage or similar viruses, further validating our choice of scaffold.

Safety Considerations

Safety Considerations

3.1 Biosecurity

DNA origami research carries biosecurity risks, as engineered DNA structures could potentially be misused, such as for sequestering biologically active molecules or producing harmful DNAzymes. To mitigate these risks, responsible research practices and safety protocols, set by a central oversight council, are essential to prevent misuse and secure materials. Additionally, we frequently used SYBR Gold, a DNA-intercalating agent with carcinogenic potential. Every use and disposal of SYBR Gold was meticulously documented and conducted following strict university protocols.

3.2 Environmental Impact

DNA origami research must also consider environmental safety, as the production and disposal of DNA-based materials could inadvertently release genetic materials into the environment. We ensured that all DNA-based materials were disposed of following university regulations to prevent environmental contamination.

Our project required the use of plastic-based equipment and disposables, which contribute to environmental concerns such as microplastic pollution. We recognise the importance of minimising environmental impact and have taken steps to ensure that processed plastic waste was sent to appropriate recycling facilities, emphasising the need for sustainable practices in DNA origami research.

3.1 Biosecurity

DNA origami research carries biosecurity risks, as engineered DNA structures could potentially be misused, such as for sequestering biologically active molecules or producing harmful DNAzymes. To mitigate these risks, responsible research practices and safety protocols, set by a central oversight council, are essential to prevent misuse and secure materials. Additionally, we frequently used SYBR Gold, a DNA-intercalating agent with carcinogenic potential. Every use and disposal of SYBR Gold was meticulously documented and conducted following strict university protocols.

3.2 Environmental Impact

DNA origami research must also consider environmental safety, as the production and disposal of DNA-based materials could inadvertently release genetic materials into the environment. We ensured that all DNA-based materials were disposed of following university regulations to prevent environmental contamination.

Our project required the use of plastic-based equipment and disposables, which contribute to environmental concerns such as microplastic pollution. We recognise the importance of minimising environmental impact and have taken steps to ensure that processed plastic waste was sent to appropriate recycling facilities, emphasising the need for sustainable practices in DNA origami research.

Legal Due Diligence

Legal Due Diligence

4.1 Handling of Nucleic Acids

International regulations on DNA and RNA, such as the Convention on Biological Diversity and the Cartagena Protocol, provide guidelines on handling genetic material. While Japan continues to refine its regulatory framework, handling DNA as genetic information is strictly regulated. However, the use of nucleic acids as components in artificial molecular systems remains undefined globally. As a result, oversight in these cases relies on review by a central authority and is managed by the responsible personnel.

4.2 Clinical Trials and Medical Applications

Medical applications are a primary focus of molecular robotics research. In our work, we reference established protocols for the development and clinical trials of other engineered therapeutics, such as monoclonal antibodies. Future clinical trials of our devices would adhere to existing ethical guidelines and comply with Good Clinical Practice (GCP) standards to ensure safety and efficacy.

4.3 Biological Weapons

The Biological and Toxin Weapons Convention (BTWC), established in 1975, serves as the main regulatory framework for prohibiting biological weapons. While artificial DNA devices are not inherently weaponized, the potential for unsupervised modifications necessitates additional oversight. Current definitions of biological weapons and toxins may not encompass these products, highlighting the need for updated legislation to address the biosecurity concerns surrounding advanced DNA-based technologies.

4.1 Handling of Nucleic Acids

International regulations on DNA and RNA, such as the Convention on Biological Diversity and the Cartagena Protocol, provide guidelines on handling genetic material. While Japan continues to refine its regulatory framework, handling DNA as genetic information is strictly regulated. However, the use of nucleic acids as components in artificial molecular systems remains undefined globally. As a result, oversight in these cases relies on review by a central authority and is managed by the responsible personnel.

4.2 Clinical Trials and Medical Applications

Medical applications are a primary focus of molecular robotics research. In our work, we reference established protocols for the development and clinical trials of other engineered therapeutics, such as monoclonal antibodies. Future clinical trials of our devices would adhere to existing ethical guidelines and comply with Good Clinical Practice (GCP) standards to ensure safety and efficacy.

4.3 Biological Weapons

The Biological and Toxin Weapons Convention (BTWC), established in 1975, serves as the main regulatory framework for prohibiting biological weapons. While artificial DNA devices are not inherently weaponized, the potential for unsupervised modifications necessitates additional oversight. Current definitions of biological weapons and toxins may not encompass these products, highlighting the need for updated legislation to address the biosecurity concerns surrounding advanced DNA-based technologies.

Intellectual Property Issues

Intellectual Property Issues

5.1 Patenting DNA Origami Techniques

Patenting DNA origami techniques can drive innovation by incentivizing research and development. However, exclusive patents may restrict access, potentially limiting the broader application of this technology across research and industry.

5.2 Licensing and Access

To maximise the potential of DNA origami, licensing agreements should promote fair access and reasonable fees, especially for academic institutions and resource-limited contexts. Excessive restrictions on licensing may impede scientific progress and limit the widespread benefits of the technology.

5.3 Use of Technology

We confirm that our project did not utilise any patented technology that is inaccessible, nor did we infringe on any existing patents. We exclusively used publicly available software, including tools like caDNAno, CanDo, oxDNA, and NUPACK.

5.1 Patenting DNA Origami Techniques

Patenting DNA origami techniques can drive innovation by incentivizing research and development. However, exclusive patents may restrict access, potentially limiting the broader application of this technology across research and industry.

5.2 Licensing and Access

To maximise the potential of DNA origami, licensing agreements should promote fair access and reasonable fees, especially for academic institutions and resource-limited contexts. Excessive restrictions on licensing may impede scientific progress and limit the widespread benefits of the technology.

5.3 Use of Technology

We confirm that our project did not utilise any patented technology that is inaccessible, nor did we infringe on any existing patents. We exclusively used publicly available software, including tools like caDNAno, CanDo, oxDNA, and NUPACK.

Societal Implications

Societal Implications

6.1 Cultural and Ethical Values

DNA origami research intersects with cultural and ethical beliefs, particularly in the context of genetic engineering. Ethical considerations involve navigating the moral boundaries of DNA manipulation and the potential implications of creating designer organisms or materials.

6.2 Economic Disparities

DNA origami research has economic implications, especially concerning equitable access to its benefits. Addressing the potential for this technology to deepen existing social and economic inequalities is essential to ensure its positive impact across diverse communities.

6.3 Research Priorities

It is crucial that society participates in setting research priorities for DNA origami to align advancements with public values and needs. Engaging the public and fostering transparent decision-making can help maintain a balance between scientific innovation and ethical responsibility.

6.4 Societal Impact

Biomolecular engineering, particularly through DNA origami, holds transformative potential in fields like medicine, enabling precise, targeted treatments for cancer, genetic disorders, and infectious diseases with fewer side effects. Beyond healthcare, DNA-based technologies can drive advancements in bioenergy, such as algae-derived biofuels and synthetic photosynthesis, promoting clean energy solutions.

However, the ability to create or modify life forms raises concerns about unintended and irreversible effects on the natural world. Critics urge caution, emphasising the need to balance innovation with restraint to avoid unforeseen consequences that could impact ecosystems and biodiversity.

6.1 Cultural and Ethical Values

DNA origami research intersects with cultural and ethical beliefs, particularly in the context of genetic engineering. Ethical considerations involve navigating the moral boundaries of DNA manipulation and the potential implications of creating designer organisms or materials.

6.2 Economic Disparities

DNA origami research has economic implications, especially concerning equitable access to its benefits. Addressing the potential for this technology to deepen existing social and economic inequalities is essential to ensure its positive impact across diverse communities.

6.3 Research Priorities

It is crucial that society participates in setting research priorities for DNA origami to align advancements with public values and needs. Engaging the public and fostering transparent decision-making can help maintain a balance between scientific innovation and ethical responsibility.

6.4 Societal Impact

Biomolecular engineering, particularly through DNA origami, holds transformative potential in fields like medicine, enabling precise, targeted treatments for cancer, genetic disorders, and infectious diseases with fewer side effects. Beyond healthcare, DNA-based technologies can drive advancements in bioenergy, such as algae-derived biofuels and synthetic photosynthesis, promoting clean energy solutions.

However, the ability to create or modify life forms raises concerns about unintended and irreversible effects on the natural world. Critics urge caution, emphasising the need to balance innovation with restraint to avoid unforeseen consequences that could impact ecosystems and biodiversity.

Conclusion

Conclusion

Research in artificial biomolecular devices represents a groundbreaking advancement with immense potential across multiple applications. However, the progress of this field brings forth a range of complex ethical, legal, and social implications (ELSI) that demand thoughtful consideration. Key issues include informed consent, privacy concerns, intellectual property rights, safety protocols, and broader societal impacts. Addressing these challenges requires a collaborative approach involving researchers, policymakers, and the public to ensure that this transformative field advances responsibly, ethically, and equitably. As the field of DNA origami and biomolecular engineering continues to evolve, ongoing dialogue and ethical guidance will be critical in navigating the ELSI landscape effectively.

Research in artificial biomolecular devices represents a groundbreaking advancement with immense potential across multiple applications. However, the progress of this field brings forth a range of complex ethical, legal, and social implications (ELSI) that demand thoughtful consideration. Key issues include informed consent, privacy concerns, intellectual property rights, safety protocols, and broader societal impacts. Addressing these challenges requires a collaborative approach involving researchers, policymakers, and the public to ensure that this transformative field advances responsibly, ethically, and equitably. As the field of DNA origami and biomolecular engineering continues to evolve, ongoing dialogue and ethical guidance will be critical in navigating the ELSI landscape effectively.

2024 USYD BIOMOD