Japan’s Fundamental Philosophy on Genome Editing Technology

Japan has reached a tentative consensus regarding regulations on genome editing technology. The best depiction of Japan’s stance on these regulations is the 2016 Interim Report on research using genome editing technology on human embryos,^{Footnote 2} which was written by the “Expert Panel on Bioethics, Council for Science, Technology, and Innovation (CSTI)” (hereafter, “the Panel”). The Interim Report is unique in that it categorized studies using genome editing according to their targeted objective (i.e., basic research vs. clinical studies). Briefly, it concludes that genome editing technology may be used for some basic research studies, but not for clinical studies.

Basic research studies that might require the use of genome editing technology on human embryos can be further categorized into those with the following four objectives:

1. 1) To elucidate the role of genes during early development and embryonic differentiation

2. 2) To contribute to the development of new treatments or preventative methods for genetic diseases

3. 3) To contribute to the development of new treatments or preventative methods for other diseases (e.g., cancer)

4. 4) Other objectives that do not necessarily pertain to illnesses.^{Footnote 3}

With regard to 1, 2, and 3, the Interim Report states, “By understanding the role of genes in early embryonic development, we may be able to gain insight that could contribute to assisted reproduction technologies or treatment of intractable congenital diseases. This insight would have social validity, not only because of the anticipated benefits, but also because we know that the role of human genes may not be fully elucidated in animals.”^{Footnote 4} However, because 2 and 3 include research studies that could be conducted without the use of human embryos, the following reservation was attached: “Depending on the methods, the research study may not necessarily require the use of human embryos.”^{Footnote 5} In addition, the underlying assumption for a type 4 objective is that genome editing technology would be used for enhancement. This was not received well, as reflected in the statement, “Currently, we cannot conclude across the board that all type 4 objectives have social validity.”^{Footnote 6} Ultimately, the Interim Report concluded that some basic research studies that “are reviewed by an institutional review board and ‘aim to elucidate gene function in early development and embryonic growth (differentiation)’ may be given approval to use genome editing technology.”^{Footnote 7}

Meanwhile, a much more restrictive approach was taken regarding the use of genome editing technology on human embryos for clinical studies. Several valid issues were raised, such as (1) the risk of off-target effects or mosaics, (2) effects on other genes brought about by genetic modification, and (3) uncertainty of the risks that would be passed down to future generations, along with concerns about whether or not these interventions into human genetics would continue to garner societal acceptance in the future, as explained here. (4) Considering that genes in their entirety represent a precious inheritance passed down to us from our human ancestors, some feel that rather than trying to avoid passing down genetic vulnerabilities simply because they create weaknesses in daily living in modern society, we should instead reconstruct our society to embrace these vulnerabilities. Serious and widespread discussion as a society is necessary to determine a clear stance on this matter.^{Footnote 8}

Given issues (1)–(4), the Panel concluded that “currently, we cannot approve” genome editing technology for clinical studies. Most relevantly, this meant that “We cannot approve the uterine implantation of a human embryo that has been subject to genome editing technology.”^{Footnote 9}

The Course of Discussion Within the Panel

The Panel was established in 2001 within the Cabinet Office’s CSTI, and is tasked with the primary objective of responding to developments in the life sciences.^{Footnote 10} To this end, the Panel conducts surveys and evaluates guidelines on issues such as the use of human embryonic stem cells or the treatment of human embryos. The Panel comprises medical researchers, bioethicists, intellectuals, and media personnel, to name a few. Within the context of the previously stated argument, the Panel considers itself “the top policy-making group in the nation for bioethical matters,”^{Footnote 11} but does not wield any power to confirm the actual implementation of its policies or the magnitude of its influence. One thing learned from discussions in Japan surrounding brain death and organ transplantation is that a grassroots level discussion that works from the bottom up is ideal for the Japanese culture.

The fundamental stance of the Panel’s Interim Report on the treatment of human embryos is consistent with the “Fundamental Principles Concerning the Treatment of Human Embryos,”^{Footnote 12} which was published in 2004 by the Council for Science and Technology, the predecessor to the CSTI. According to this document, “Unlike other cells in the human body, the human embryo holds meaning as a sprout of human life, and it is therefore ethical that we show respect and treat it with extreme care.”^{Footnote 13} This position that emphasizes the aspect of human dignity appeared for the first time in a March 2000 publication entitled “Fundamental thoughts regarding human embryo research focused on human embryonic stem cells,”^{Footnote 14} and led to the creation of guidelines for human embryonic stem cells in September 2001,^{Footnote 15} which approved the establishment and use of these cells.

Thereafter, with rapid advances in genome editing technology, the Panel convened 14 times beginning in 2015 to conduct hearings with researchers, scholars, the Japan Medical Association, and other relevant academic societies, and holds many discussions among the Panel members. The main publication denoting the outcomes of these discussions is the “Interim Report,” which was released at the Panel’s 97th meeting in April 2016.

All assumed that the Interim Report would be scrutinized and then authorized to be made into guidelines or even a law. Instead, confusion broke out. Differences in opinions surfaced, creating a division between the Panel and academic societies involved with genetics (Japan Society for Gene and Cell Therapy, The Japan Society of Human Genetics, The Japan Society of Obstetrics and Gynecology, and Japan Society of Reproductive Medicine). The Panel asked the academic societies to create regulations that would function as “self-governance by the community of researchers.”^{Footnote 16} The academic societies pushed back, saying that self-governance by the community of researchers alone is limited in viability, and that the national government should take initiative and create regulations concerning genome editing technology.^{Footnote 17} However, the Panel held its ground, maintaining that its role was one of “cooperation,” and urged the academic societies to ramp up their efforts to increase the validity and their ownership of regulations pertaining to genome editing technology. The academic societies felt the Panel’s stance represented a “cop-out” of sorts that left all the important decisions to the academic societies, stating that “others seem to think the academic societies are self-regulating these matters.”^{Footnote 18} Distrust toward the Panel grew among the academic societies, and eventually, the joint committee with the academic societies disbanded.^{Footnote 19} It was at this point, following this course of events, that Chief Cabinet Secretary Suga announced at the April 19 press conference that “the Japanese government must become responsibly involved in genome editing technology.”

Residual Ambiguity in Japan’s Response

The unstable foundation of Japan’s bioethics regulations has led to these indecisive bioethics in Japan; namely, to our moral moratorium on bioethical issues.

The “Fundamental Principles Concerning the Treatment of Human Embryos” defines a human embryo as “neither a ‘person’ nor a ‘thing.’”^{Footnote 20} As such, although an embryo may not be a “person,” it does represent an existence—described as a “sprout of human life”—that requires particular respect in a society in which maintaining so-called human dignity is valued.^{Footnote 21} At first glance, it would seem that this clarification finally provides an appropriate status to human embryos, along with a foundation that can offer the necessary protection. There is certainly some truth in that. On the other hand, we now have to accept this ambiguous being that is “neither a person nor a thing.” Creating this mysterious being adds no more meaning to that which is in the gray zone; that is, that treatment of fertilized human embryos should be evaluated on a case-by-case basis. Admittedly, this definition linguistically functions to convey the message to the Japanese people that human embryos differ from regular cells, and that we should treat them with more consideration and respect than that given to somatic cells. Aside from that, however, defining human embryos as the “sprout of human life” only makes it seem as if a decision on the moral status of human embryos has been made, when really, nothing has changed at all.

Much like the Fundamental Principles, the Interim Report is also quite vague about regulations on genome editing technology. For example, although the Interim Report does not allow genome editing technology to be used in clinical studies, it states that a portion of basic research studies may receive approval to use genome editing technology. In the final analysis, however, wouldn’t that “portion of basic research studies” be determined on a case-by-case basis anyhow? Obviously, flexibility is a good thing. However, if flexibility is the sole feature of this set of regulations, then tough decisions concerning urgent ethical issues will be forced upon researchers and clinicians on site, leading inevitably to a dysfunctional system. This is precisely why academic societies requested government involvement and responsible policymaking for regulations on genome editing technology. If the Panel is truly “the top policymaking group in the nation for matters related to bioethics,”^{Footnote 22} then it is even more appropriate that it submit a thoughtful, decisive policy that offers strong support to researchers. Moreover, if the Panel wishes to maintain a truly “cooperative” role with researchers, then this is even more reason why it should construct policies that can also be backed up by some ethical theory; in fact, this could be exactly the type of support and cooperation required of it.

Summary and Future Directions

The situation has become increasingly muddled. At the Panel’s 104th meeting (May 2017), the Secretariat (the government and the cabinet) suddenly proposed the reconsideration of the “Fundamental Principles Regarding the Treatment of Human Embryos,” which had thus far been considered a major premise throughout these discussions.^{Footnote 23} In response to such a drastic change, some members of the Panel complained that this proposal seemed to have come out of the blue, and that it veered the discussion off the path that had been taken for more than a year.^{Footnote 24} In the midst of that, the Science Council of Japan, which is a group of researchers in all fields of research (not just medicine) spoke up on September 27, 2017. In that, they proposed to the Japanese government that, with regard to the application of genome editing technology to reproductive medicine, the nation should create the bare minimum guidelines and consider the possibility of legislation; and with regard to basic research, the Ministry of Education, Culture, Sport, Science, and Technology (MEXT) and the Ministry of Health, Labour, and Welfare (MHLW) should create appropriate guidelines. It is unclear how the government will respond to this movement in the discussion; therefore, the gap between the researchers and the government remains unfilled.^{Footnote 25}

Perhaps it is time for Japan to stop putting off these hard decisions through vague and indecisive tentative conclusions about bioethics, application of relevant technologies, and treatment of human embryos. Researchers in the arts and humanities need to be included in the grassroots level discussion, as their new insight would be invaluable in creating a sound and thoughtful basic policy. The creation process of regulations for genome editing technology has been given a fresh start, and Japan is in the preparation stage. The need for widespread discussion is increasingly evident. The Japan Association of Bioethics will hold their conference in the winter of 2017, and symposia pertaining to the ethics of genome editing technology are already on the docket. Grassroots level activities have begun.