Now I get it! ELSI and Genome Editing

Genome Editing and Society--Thinking about ELSI (Ethical, Legal, and Social Issues)

1. What is ELSI?

When new science and technology are introduced into society, there are many benefits, such as improvements in quality of life and advances in medicine. However, the newer and more groundbreaking these scientific advancements are, the greater the changes they will have on our world, creating novel situations that cannot be easily understood by conventional ways of thinking. In order to address exactly such issues, the life sciences have been increasingly focusing on ELSI (Ethical, Legal, Social Issues) in recent years.

"The Human Genome Project" in 1990 brought a lot of attention to ELSI. This project aimed to decipher the entire DNA sequence in human cells, in other words, all of human genetic information, thereby contributing to the development of medicine and other human endeavors. At the same time, however, because of the sensitive nature of the genetic information, problems arose that went beyond the realm of science, such as the possibility of discrimination and the protection of personal information. As such, a forum was created where not only medical professionals, patients, and natural science experts, but also scholars in sociology, ethics, law, philosophy, and other fields, as well as governments, businesses, and citizens could come together to discuss these issues.

2. What is Genome Editing?

What exactly is genome editing technology? First, let us briefly review what a "genome" is. Each of the many cells in our body contains a substance called DNA (deoxyribonucleic acid). The important part here is called the "base"(adenine, guanine, cytosine, and thymine), and the genetic information is determined by these four "strings," or sequences. The term "gene" refers to the part of DNA that contains information that serves as a blueprint for living organisms. The word "genome" is a combination of the words "gene" and "ome," meaning all the information from end to end of A, G, C, and T, including the parts that are not "genes," i.e., the totality of genetic information in the substance called DNA.

"Genome editing" is a technology that modifies, or alters, the genome. A similar term that we often hear is "genetic modification," but there is a slight difference between the two. When DNA is cut, a repair function is activated, but if the same part of the DNA is cut repeatedly, an error occurs in the repair process and a part of the DNA is left missing. This is what genome editing intentionally does. Incidentally, DNA repair errors themselves occur in nature as so-called "mutations". Therefore, mutations caused by genome editing are similar to "mutations" in the natural world. On the other hand, "genetic modification" is different, as it incorporates genes from another species that the target organism did not originally possess. However, "genome editing" can also incorporate genes from other species into the cut portion　"genetic modification ", thus combining the same level of modification as mutation in nature with techniques.

Currently, the most widely used technology for genome modification is CRISPR-Cas9, which can perform editing with extremely high accuracy. However, there are various controversies concerning its use, such as the side effects known as "off-targets," which are the unintended consequences of gene modification. Although the targets of genome editing may be plants and other non-human species, genome editing for humans in particular is strongly linked to the ELSI issues that have evolved since the beginning of the Human Genome Project.

3. Importance of basic research on human genome editing

The targets of human genome editing are classified into somatic cells (other than germ line) and germ line (fertilized embryos, eggs, sperm, etc.). For each of these two categories, there are two directions in research: basic research to obtain scientific knowledge and clinical application in medicine.

In the case of basic research, somatic cells are widely accepted for use, but the use of germ line cells varies from country to country. In the United Kingdom, the United States, and China, the use of somatic cells is mainly permitted under national regulations; while in France and Germany, it is prohibited by law. In Japan, the Japanese government has held a number of meetings in recent years to discuss the issue. At this point, although there are still areas that need to be debated, the policy is to allow the use of somatic cells after review on a case by case basis.

More careful discussion is required when considering the use of germ cells. This is because a fertilized human embryo is a "germ of life" that has the potential to be born as a human being. However, while the ethics of "human dignity" is a major issue, basic research using fertilized human embryos has a very important role to play. By observing how genes work in the early stages of the formation of the human body, it is possible to learn many things about the causes of pathological conditions and the development of treatments for hereditary diseases. It is precisely because such basic scientific research is being steadily conducted that the path to medical development and clinical application is opening up.

4. Challenges for clinical application

Expectations about the treatment and prevention of diseases may rise when one hears about the clinical application of genome editing in humans. On the other hand, however, the impact on life and society will be significant, and this is an issue that must be considered from a variety of perspectives beyond basic research.

First of all, clinical application to somatic cells involves the use of genome editing technology on the patient's own somatic cells to treat hereditary diseases, cancer, or infectious diseases. In this case, ethical issues such as the difference between medical treatment and the "enhancement" of the body come into play.

In the clinical application to germ cell lines, genome editing will be performed on fertilized human embryos that have not yet been born but can be considered "sprouts of life". In this case, the effects of the genetic modification will be felt not only in the mother's womb but also across generations. Since we don't know whether or not the fertilized human embryos to be treated can be treated, there are serious concerns about long-term safety in the future. There is also the possibility that genome editing could limit the diverse ways of being of future generations according to the standards of today's society. This, in turn, could lead to a kind of eugenics for human beings in the future.

In particular, the pros and cons of clinical application of assisted reproductive technologies have been discussed around the world in recent years and in 2019 a committee was established by the WHO. In Japan, as assisted reproductive medicine has shown remarkable development in recent, there have been calls that self-regulation by academic societies alone is not sufficient for the medical application of genome editing in fertilized human embryos. To address this situation, an expert committee was established by the Ministry of Health, Labor, and Welfare in 2019, and in January 2020, a report was published stating that it is necessary to enact a law regarding the clinical application of genome editing in fertilized human embryos.

Despite the need for caution, the benefits that can be brought about through the clinical application of genome editing are enormous and society as a whole - not simply the scientific community - needs to seriously consider the appropriate use of this technology.

5. Communication with Society

Currently in Japan, public open house events are being held in collaboration with the Cabinet Office, universities, scientists, or institutions such as the National Museum of Emerging Science and Innovation in order to increase the understanding of genome editing technology within society. This is the first step towards advancing the public debate.

These activities cannot succeed overnight, but must be steadily built up while taking into account a variety of perspectives and experiences. One issue that is often raised is the "lack model," which assumes that the general public is critical of new science and technology because of a lack of expertise. This model assumes that a one-way communication from experts to the general public will solve the problem. However, many survey respondents indicated that because they are able to consider various viewpoints now that they are more knowledgeable about genome editing, they are no longer able to easily come to conclusions about the use of genome editing. Of course, we should not underestimate the role of experts in helping citizens become scientifically literate. What is important is to build on this relationship to create more interactive forms of communication.

Another question that is often raised is whether it is only citizens with a high interest in science who participate in the events. In this regard, a variety of efforts are underway, such as notifying high schools and other institutions of the events, holding events targeting high school students, and providing opportunities for them to experience discussions concerning genome editing from an early stage.

In any case, the most important thing is to deepen the understanding of genome editing and to develop the discussion on its use in society as a whole. We need to deepen our understanding not only of genome editing in humans, but also of its application in plants and other organisms. What do you think? We would like to hear from a variety of people from various backgrounds in order to help make a better society for us all.

（Hiroki Hashimoto）