ELSI

Introduction

On this page, Bilayer-DNA-Bilayer (BDB) and Bilayer-Gel-Bilayer (BGB) are discussed from the perspective of ELSI. ELSI stands for Ethical, Legal, and Social Issues^[1]. The development of science and technology brings great benefits to society. On the other hand, the development has at times caused serious problems for both society and the environment. Therefore, when developing new technologies and implementing them in society, it is necessary to consider their impact on society from an ELSI perspective in advance. We have a responsibility to consider a better future by examining new technologies and ELSI with experts in various fields and people in various positions.

Ethical Issues

BDB (Bilayer-DNA-Bilayer) and BGB (Bilayer-Gel-Bilayer) will be discussed from the perspective of bioethics and dual use.

〇Perspective 1: Bioethics

BDB and BGB are constructed by phospholipids and DNA. Phospholipids and most DNA are chemically synthesized, so there are no ethical issues. While, the scaffold strand in DNA origami used for tubulation is M13mp18, a circular single-stranded DNA derived from M13 phage. Although M13 phage is a virus generally not considered an organism, the M13mp18 was produced by infecting E. coli with M13 phage. Since E. coli is an organism, this point is open to ethical debate. For this reason, this section particularly addresses the ethical considerations of using E. coli.

In the course of infecting E. coli with M13 phage, the E. coli may die. In other words, it can be said that this intentionally infects a living organism with a virus and causes it to become sick or die to produce the desired DNA. Some people may feel that this is not bioethically appropriate. On the other hand, using many microorganisms keeps the economy going, so some may feel that this is not bioethically problematic or unavoidable.

Then, how would the use of E. coli be considered from a utilitarian perspective? In discussions of bioethics such as animal husbandry, the conversation often revolves around the perspective of utilitarianism. Utilitarianism focuses on the greatest happiness for the greatest number, and minimizing suffering is good^[2]. E. coli is a single-celled organism and It is commonly believed that it has no pain, suffering, or emotions. Thus, from a utilitarian perspective, using E. coli presents no ethical issue, and its use can be considered acceptable.

What about the perspective of land ethics, then? In The Rights of Nature, Roderick Nash states that land ethics subjects all life forms to ethical consideration^[3]. Hence, E. coli is an ethical consideration, and someone might argue that the use of E. coli should be stopped.

There are a variety of philosophical values and ideologies that determine the extent to which life is covered by ethics. People from various perspectives must engage in a society-wide dialogue on the relationship between our social system and life.

〇Perspective 2: Dual use

The civilian and military uses of science and technology are closely linked and often inextricably linked. As a result, science and technology can be used militarily in ways unintended by the developers, endangering society. Scientific and technological advances have the potential to improve society and to pose new security threats. This ambivalence is referred to as the dual use dilemma.

At present, BDB and BGB consider the possibility of dual use to be low. This is because BDB and BGB are simply membrane structures and do not function by themselves. However, from various perspectives, BDB and BGB have been confirmed to have higher stability than conventional liposomes, and have the potential to expand the field of nanorobot activity in the future. The possibility of nanorobot research being diverted to military use cannot be denied. Therefore, we believe that it will be necessary to consider the dangers of dual use of nanorobots using BDB and BGB in the future. Open discussion with the public on the development and use of nanorobots is needed.

Legal Issues

We do not believe that BDB and BGB in this project have room to cause legal problems at this time. However, there are things to consider for the future.

No living organisms are used in this project. In addition, BDB and BGB use DNA that does not contain genetic information in its structure.

However, the scaffold strand in DNA origami used in the tube is M13mp18, a circular single-stranded DNA derived from M13 phage. This scaffold strand contains the genetic information of the phage; in the DNA origami, M13mp18 was only used as a scaffold to form the structure, so the genetic information is not transcribed or translated. Therefore, this project is completely unrelated to genetic modification or genome editing and is not contrary to the Cartagena Protocol^[4] or any other treaties or laws. However, the use of DNA in this DNA origami could be confused with genetic manipulation or genetic modification, which could lead to misunderstandings about safety. Hence, it is important to provide correct information to society and conduct educational activities.

In addition, if a product using BDB and BGB is damaged, the responsibility for the product must be clarified. For example, if a nanorobot using BDB and BGB is damaged or malfunctions in vivo, it may lead to liability issues. When implementing in society, it is necessary to establish laws and guidelines that are appropriate not only for the stakeholders, but also for those who are not involved.

There is a certain amount of potential for medical disparities, environmental issues, and problems related to making and accountability when BDBs and BGBs are put into practice in the future.

〇Medical Disparities

We are considering the future of in vivo use of BDB and BGB. However, at this time we have not conducted any experiments on the biocompatibility of BDB and BGB. We believe that the biocompatibility of BDB and BGB is relatively low, but cannot be completely ruled out. In particular, it is necessary to seriously consider the extent to which DNA and DNAhydrogel are degraded in vivo and how they are absorbed and excreted.

Our experiments also showed that BDB and BGB have higher stabilities than conventional liposomes. This may allow liposome products to be supplied to a larger number of patients at a lower price, without being affected by economic disparities. However, depending on the drug encapsulated inside the liposome formulation, the price may not decrease. Thus, liposome drug products with high stability cannot solve all medical disparities, and the need to investigate the actual situation of medical disparities and establish a system to solve them will not disappear. Citizens from various standpoints should communicate with each other and for society as a whole to consider improving medical disparities.

〇Environmental Issues

We believe that the environmental impact of BDB and BGB is small. Currently, environmental problems caused by man-made products, such as the microplastic problem, are becoming more serious. The reason for this is that many of them do not biodegrade in the environment and remain in the environment for a long period. Liposomes, on the other hand, are made of easily degradable materials and are being studied to allow them to remain in the environment for a certain period. Although they have higher stability than liposomes, BDB and BGB are made of biodegradable materials. Hence, they do not remain in the environment. However, if liposomes with very high stability are developed in the future, or if vesicles are made of non-biodegradable materials, they may have a large environmental impact. For social implementation, it is necessary to fabricate vesicles from biodegradable materials and incorporate a function that allows vesicles to self-disintegrate for easy biodegradation when they have completed their role.

Our BDB and BGB are designed to be released into the ocean. In the ocean, substances can affect entire ecosystems through processes such as bioaccumulation. The marine organisms on our tables can be the endpoint of enrichment. Thus, the nature of the substances released into the ocean should not be underestimated; a thorough study should be conducted beforehand to determine the extent to which BDB and BGB adsorb toxic substances such as heavy metals and heavy oil.

It is also necessary to consider the effects of nanorobots that are designed to operate in water if they enter the bodies of aquatic organisms. It is especially important to determine whether the impact on marine organisms, which are feared to be extinct, is minimal.

〇Safe Production and Accountability

The structure of BGB and tubulation uses cholesterol-modified DNA The cholesterol-modified DNA used in BGB and tubulation is very small amounts. Therefore, even if a person were inoculated with BGB or tubulation, cholesterol would not have any adverse effects on the human body. However, since cholesterol is generally recognized as a factor that causes atherosclerosis, it may give rise to the misconception that BGB, tubulation, and cholesterol-modified DNA cause atherosclerosis. When dealing with cholesterol-modified DNA, including us, sufficient explanation to the public is required.

Also, even if theoretically safe, it may pose a risk depending on the producer or production company. In this project, chloroform is used in the process of making lipid films. Chloroform is a highly volatile, toxic, and carcinogenic substance. In our fabrication process, chloroform is completely volatilized in a clean room draft, and our BDB and BGB are safe.

Also, experimenters should use the least hazardous substances possible with an understanding of their purpose to prevent accidents. In this project, sugars such as glucose and trehalose are used for the inner and outer solutions of liposomes, BDB, and BGB to ensure safety.

However, we cannot guarantee the safety of those prepared by third parties at this stage. We have a responsibility to establish BDB and BGB and liposome preparation materials & methods that are safe for anyone to prepare, and to publish and explain their safety so that the public can understand them.