Regulating cell lives in Japan: avoiding scandal and sticking to nature

Abstract

The life sciences in Japan have been reappraised since late 2007 developments in human induced pluripotent stem (iPS) cell research. This article analyzes how Japan's research on fetal cells, human embryonic stem cells and iPS cells is co-produced with policies on funding, sourcing, bioethics, international regulation, and intensifying international competition. I argue, first, that regulation of human embryonic stem cell research (hESR) in Japan, though attempts have failed to engage the public, has been shaped through the leverage of social groups; and, second, that the 2007 reappraisal of hESR and the efforts made to advance to clinical applications in 2008 reflect a change in the orientation of policymakers toward regulation. Using anthropological notions of natural symbols, the article shows how the regulatory emphasis on what is regarded as ethical in the case of hESR has been confused with “safe” procedure, and how a risk-averse change in favor of iPS cell research according to stem cell scientists actually formed the reckless option.

Keywords:

• stem cell research
• Japan
• iPS
• purity and danger
• bioethics

Introduction

This article asks how regulation of human embryonic stem cell research (hESR) in Japan was shaped and how gametes, pluripotent cells and life values were embedded in discourses on procreation, including discussions on human embryonic stem cells (hESC) and induced pluripotent stem (iPS) cells. Because the former are sourced from embryos, and the latter created from somatic cells, hESC have been a source of contention in Japanese society, in contrast with iPS cells, which at the time were claimed to be identical to embryonic stem cells. The controversy around hESR led to a stringent regulatory regime for hESR, where regulation stipulates the respectful treatment of hESC as the “germ of life” (Sleeboom-Faulkner 2008). After the breakthrough in human iPS cells in 2007, a major shift took place in public opinion in favor of iPS cells, partly because iPS cells were seen as a product of Japanese science and partly because of their ethically uncontroversial nature compared to hESC (Editorial 2008, Liu 2008, Shineha et al. 2010).

Japan is often seen as an a-religious country, as historically it would never have attached great value to the “human rights” of the embryo or even a small child (Shimazono 2008, interview Shimazono 1). Nevertheless, Japan is crowded with religious notions and institutions, which express religious and spiritual concern. The newspapers expressed such concern:

The creation of a legal framework in the form of a comprehensive basic law on bioethics in order to preserve the sanctity of life while not taking the edge off pioneering science is an urgent matter. (Nikkei Shinbun [Japan Financial Daily] 2002)

The question arises, then, of how the notion of the sanctity of life is related to the respect of pluripotent stem cells in a country that is widely advertised as being a-religious. In this article I argue that the context for the regulation of hESR in Japan is that of an ageing welfare society (see Moffett 2003, Masaki 2006), aiming to remain at the world's forefront in life sciences developments, while trying to cater for popular notions of Japanese culture.

Japanese policymakers have tried to open the way to human therapeutic cloning through the anti-cloning law (Kayukawa 2003) and by redefining the embryo as “the sprout of life.” The power to “name” life here (de Certeau 1984) can be seen as the power to define what life means, who respects it, and who violates it. Defining what is respect for some forms of life, rather than others, and in which particular ways, rather than others, has enabled the regulation of hESR. Japan's history of eugenics, however, more crudely privileged certain forms of life over others, and, as explained below, has left widespread anxiety regarding reproductive technology, although feminists, democracy and human rights valorizations of life have steadily gained political weight. This article shows how contemporary policy making on stem cell research has largely been influenced by the historical symbolism of ethical concepts rooted in Japanese society, including the modern symbolism of “scientific advancement” and the natural symbolism of the embryo as “the sprout of life” and “respect for embryonic stem cells” (though not for iPS cells).

Japanese dominant discourses emphasize the importance of the notion of the group and symbols of nature, such as purity and danger (Valentine 1990). According to Mary Douglas (1992), symbols do not just dramatically express the social order and legitimize social functions, they are also modes of communication. In Japanese stem cell governance, rather than “rational” notions of scientific risk associated with the West (Beck 1992), it is the danger associated with scandal that the regulatory bureaucracy regards as a threat. In dominant discourses on Japaneseness (Nihonjinron) the violation of what is regarded as “natural behavior” through modernization and science and technology forms a menacing source of danger to Japanese culture (cf. Dale 1986, Sleeboom 2004, Robertson 2005). In short, political decision making around hESR is influenced by the perceived need of “scientific progress,” and through socio-cultural notions of what is “natural” and “healthy” for society.

Natural symbolism is also relevant to understanding the strictness of regulatory implementation of hESR in Japan. Although audits and monitoring practices are important forms of social control in the Japanese life sciences, these notions cannot explain why the regulation of hESR became a sore issue in the halting field of hESR, in contrast with the immediate resolve to support regulatory leniency regarding iPS cell research. Other works have discussed pollution symbolism and boundary making in the context of safety and ethics in science research practices in laboratories (Franklin 2003, Wainwright et al. 2006, Sleeboom-Faulkner 2007, 2010a, Stephens et al. 2008). This article substantially extends these approaches by illustrating how natural symbolism and notions of danger in society have imbued science regulation and its implementation with emotional meaning.

This study draws on data gathered during 10 weeks of fieldwork in 2006 and six weeks in 2008 to gain insight into valuation of reproductive materials and potential scientific discoveries. The fieldwork consisted of archival research and semi-structured interviews with 40 stem cell scientists, 25 policymakers, students, eight housewives, and six religious professionals. The three latter groups were chosen to gain insight into the views of social groups, whose rough equivalents in Europe and the US object to hESR. Data obtained from interviews with stem cell scientists pertain to their views of regulation, its implementation, and public discussion, while data from interviews with students, housewives, and religious professionals served to obtain insight into popular understandings and support for embryo research and iPS cell research. Interviews with policymakers yielded insight into how various regulators and committee members deal with the diversity of public views and among scientists and with hESR regulation and its implementation. These data made the author aware that it was the fear of scandal and reputation blemish rather than the generally controversial nature of hESR that was problematic in the regulation of hESR in Japan.

Pseudonyms have been used so as not to attract attention to individuals, although none of the interviewees, when asked, expressed objections to being cited in articles. Interview questions concerned knowledge about, and the ethical issues of, regenerative medicine. In the case of scientists, they also included questions about the regulation of the research and work in the laboratory. Interviews took place mostly in the Kansai and the Kanto regions, where the main stem cell research (SCR) hubs are located, and interviewees were approached through contact networks, starting at the twelfth meeting for Genetic Engineering and Regenerative Medicine on 22 April 2006 in Kyoto. After sketching the historical background of abortion, and regenerative medicine, and summarizing official and public views on hESR and iPS cell research, the article analyzes the decision making underlying regulatory changes regarding hESR in Japan.

Bioethical confusion: regulating birth and lengthening life

In this section I argue that the bioethical confusion around embryo research in Japan needs to be, at least partly, understood in the historical context of both birth and ageing in Japan as a modern welfare state. A glimpse of Japan's eugenic history on abortion places the embryo in a clearer bioethical light. In Japan, induced abortion was not subject to prohibition until the Meiji reforms in 1868, when it became a criminal offence. In the 1930s, the eugenic law was introduced, making abortion a crime against Japan. It was relaxed in 1948 and, after the baby boom of the 1950s, abortion was allowed under various conditions. With Japan's modernization an alteration took place in Japan's family structure from the family household (Ie) to the nuclear family (small families, individualized decision making) (Matsubara 1998, Norgren 2001). From the 1990s, Japan's nuclear families were encouraged to give birth, and in vitro fertilization (IVF) became subsidized. In Japan's fast-ageing society of today the government and companies such as Matsushita financially encourage large families (Moffett 2003, Masaki 2006). In other words, a shift took place in the debate from a focus on the destruction of embryonic life (mass abortion) to an emphasis on the creation of embryos in a welfare society that is ageing and paying for families to have offspring.

Since the 1960s, contradictory trends in society, as a result of population policies, modernization and developments in reproductive technologies, complicated current discussion on the status of the embryo and abortion. First, though mass abortion takes place (over 300,000 induced abortions per annum), in principle induced abortion is still illegal under the penal code, which means that it has not yet been decriminalized. Since the 1970s, the increased abortion rate has been accompanied by the flourishing of mizuko kuyo, rituals for the spirits of aborted fetuses (LaFleur 1992, Hardacre 1997). Complex feelings about abortion and the taboo on discussing it openly kept most people out of the discussion. Second, the development of new reproductive technologies, such as IVF and intracytopla smic sperm injection (ICSI) made artificial birth easier: currently over 1% of all newborns are brought into the world through IVF (Sato and Iwasawa 2006). But, although IVF aims to bring embryos to fruition, it also tends to destroy some in the process. Undergoing IVF, apart from being an emotional, financial and physical burden, raises difficult bioethical dilemmas: it requires potential parents both to highly value potential embryos and oocytes, and to be prepared to discard some at the same time. Third, at the level of society as a whole, although IVF adds some extremely desired members to the population, mass abortion seems to devalue embryos and fetuses of up to 12 weeks of age. The latter trend made possible the practice of using discarded embryos in research to find cures for diseases and issues related to an increasingly ageing population, a goal explicitly mentioned in the Millennium Project. In this context, scientists ask why strict guidelines on oocyte donation are needed if annually over 50,000 oocytes are being discarded. But according to women's organizations such as Soshiren, these questions only add to the bioethical confusion around reproductive policy making and behavior (interview Nakauchi, 9 June 2006). This constellation of factors makes it hard to either fully support or reject research based on embryos.

This article argues that the bioethical confusion can be partly explained through the friction between conflicting notions of Japanese civilization, purity, naturalness, and the aversion to scandal, the adoption of pro-natal and ageing population policies, and a wish to be among the world's most advanced scientific powers. The friction between these notions has not led to widespread public engagement in the field of hESR. About a quarter of the interviewees – including scientists, housewives and policymakers in equal proportions – spontaneously noted in this context that Japan does not excel at holding bioethical debate.1 The government, companies, communities and families, as a rule, are afraid of scandal. Japanese dominant discourse (Nihonjinron), which greatly emphasizes cleanliness and purity, ideologically rooted in its historical traditions, avoids reputational blemish and scandal (omote) (Valentine 1990). Talk about embryos remains taboo among the wider public, and procedures that deal with them are experienced as most sensitive.

Official stances on hESR

To stimulate economic activity after Japan's economic slump in the 1990s, the Japanese government set up the Millennium Project, a mega-project designed to encourage the innovation of science and technology, stressing the role of the life sciences. This political direction led to generous financial support for SCR in the universities. At the same time, much attention was paid to the regulation of bioethical issues associated with the research and applications in the life sciences. Rather than building regulation on “rational” categories of risk, regulatory authorities have been influenced by traditionally highly valued concepts of nature and the avoidance of scandal.

On 25 September 2001, Japan's Ministry of Education, Sports, Science and Technology (MEXT) under the Koizumi government implemented the decision to allow the creation of human embryonic stem (hES) cell lines for SCR. The research generated a bioethical need to redefine such embryos officially. A new concept of the embryo as the “germ of life” (seimei no hooga) was put forward, a notion that made respect for the embryo mandatory, especially among researchers in the laboratory (Kayukawa 2003, Morioka 2006). Simultaneously, it was decided to uphold the principles that the human embryo should not be created for research purposes and human embryos should not be destroyed for research purposes alone (cf. MEXT 2009). The new regulation allowed the isolation of hES cell lines in the Institute for Medical Frontiers in Kyoto, by Nakatsuji Norio and his team.

Only a few years later, in 2004, the Cabinet's Council for Science and Technology Policy (CSTP) voted for the use of hES cells from aborted fetuses in the laboratory and in clinical research. Its Bioethics Expert Panel decided to allow the creation of guidelines for therapeutic cloning, which were formulated in the Interim Report Working Group of Therapeutic Cloning in June 2006. Therapeutic cloning would only be allowed under strict conditions: only if the objective of research using hES cell lines was to cure serious diseases, and only if detailed informed consent procedures using a coordinator would be followed (Cyranoski 2005, Nakatsuji 2007). Furthermore, the donation of oocytes could only take place if derived from IVF treatment, frozen, or removed from the ovaries; the donation of somatic cells had to have guaranteed anonymity; the research institution in question had to have proven its high standards beforehand, such as having experience with animal cloning, hES cell derivation; it had to guarantee the participation of a researcher with experience in cloning primate embryos; and it had to apply appropriate ethical review. These conditions created a high threshold for candidate institutions to attempt therapeutic cloning. Even after three years, the Ministry of Health, Welfare and Labour (MoHWL) Committee for Human (somatic) Cloning in a Clinical Setting, led by Nakahata Tatsutoshi, found it impossible to develop regulation for the clinical application of hES cells: only for somatic stem cell research applications was regulation completed. One of the reasons for this was the scandal brought about by the discovery of fetuses among the refuse in Yokohama City Hospital (Yokohama Kokuritsu Byooin) (Sleeboom-Faulkner 2008), for subsequent surveys showed that similar practices were taking place in other hospitals in Japan. In short, the definition of the embryo as the “sprout of life,” mandatory respect for the embryo, a meticulous implementation of the regulation by the bureaucracy, and a fear of public scandal turned hESR into a moral danger zone for scientists and regulators alike.

Public stances on hESR

In contrast to the impressions evoked by broad claims of the unity of the Japanese stance on bioethics (Robertson 2005), interviews revealed that Japanese views on the embryo, gametes and the fetus vary greatly. Views on the embryo range from regarding the embryo as the “germ of life” and the seed of life, to the embryo as sacred among Japanese sects. Views on the treatment of gametes include no objection to the donation of oocytes, a forbidding attitude to oocyte donation, and the attribution of kokoro or mind to ova (see also Sleeboom-Faulkner 2010b). Although many Japanese, in particular scientists, say that fetuses have no spirit, many women partake in ceremonies for deceased fetuses (Mizuko kuyo) (LaFleur 1992). But it is not entirely clear to what extent this means that women regard the fetus as having a spirit (Sleeboom-Faulkner 2010a).

The public discussion on hESR in Japan is limited (Kato 2005). Only the views of a few groups, such as the anti-eugenics network (which broke up in 2007), the Soshiren (Japanese women's movement), some patient movements, and religious groups were voiced in the media. Multiple positions on hESR coexist in Japan, varying from support for SCR to help handicapped people, support for SCR for infertility treatment, opposition to SCR when regarded as too artificial (fuzhizen [unnatural]) and too expensive, opposition to abortion and the interhuman transfer of biomaterials for religious reasons, and opposition to hESR as protest against the donation of reproductive materials by women (see Sleeboom-Faulkner 2008, Kato and Sleeboom-Faulkner 2009). But even though ample disagreement exists about hESR in Japanese society, and even though the government has invested heavily in national debate on the subject, public debate remained low key.

The low-key nature of the debate, according to group discussions held in December 2008, was due to the general aversion among Japanese people to “unnatural” practices and “high-tech” and “commercial” attitudes towards life, a view also voiced among some members of disabled movements (interview Chiba, 1 June 2006). Although approximately 30% of the interviewees viewed human fertilized eggs as “human lives,” over 40% said that they would approve their use in research conducted to advance the medical science. What is regarded as problematic by most, however, is not so much the principle of using embryos or oocytes in research, but the idea of mainly focusing on high-tech methods for extending the lives of the ailing elderly, rather than improving the quality of life during the “natural” life span.2 Another relevant point is that approximately half of the scientists (21) and nearly all non-scientists (25) said that the donation of reproductive materials should take place only to help kin. Potential donors also speak of the motive for embryo donation in terms of kin. Thus, research shows that couples asked to donate embryos usually respond in terms of “motherhood ethics” justifying the answer in terms of what is “best for the child” (Kato and Sleeboom-Faulkner 2011). The commercial incentives and the impersonal nature of the research were most mentioned as the reasons for the aversion (kirai [dislike]; iya [disgust]; fushizen [unnatural]; ayashii [dubious, suspicious]) felt against the use of reproductive materials in science applications. Central here then is the controversial nature of the disentanglement (Callon 1998) of reproductive material from the intimate sphere and its insertion into a commercial and impersonal economy.

IPS cells: bioethical relief and a boost to Japan's national pride

When Yamanaka Shinya and Kazutoshi Takahashi in 2006 published their research on iPS cells derived from mice, not many Japanese had heard of stem cells and pluripotency. In 2006, interviewees revealed that most laypeople had not heard of stem cells, though some could relate the subject to the Hwang Woo-Suk scandal around the fabrication of research data and unethical oocyte donation in South Korea (Sleeboom-Faulkner 2008). But according to a survey conducted by Shineha et al. (2010), over 80% of Japanese in 2008 had an opinion on regenerative medicine and expressed understanding of the significance of “pluripotency.” Similarly, interviews I conducted indicated an almost universal awareness of the meaning of iPS cells and pluripotency among housewives and students.

Induced pluripotent stem cells (iPS cells) are products of the direct reprogramming of somatic cells to an embryonic-like state. This process involved the introduction of a limited set of transcription factors (initially four) and feeder culture (under ES cell conditions) to “fool” the somatic cell into reprogramming. Although Yamanaka and Takahashi, in October 2006, were the first to “discover” iPS cells, when they tried to apply their technique to human somatic cells, they had competition from Jaenisch's team of the Massachusetts Institute of Technology (MIT, USA), who published their laboratory's research results in the same month, in November 2007.

IPS cells discovery in Japan was received with great enthusiasm. It was front-page news for weeks, and was discussed in all newspapers, on TV and on the Internet. IPS cells were advertised as a bioethical cure for old-age diseases, not requiring oocytes or embryos. Compared to somatic cell nuclear transfer (SCNT), iPS cells promised to produce pluripotent cells with the same traits as human ES cells: pluripotency was the buzzword in the media. IPS cells were portrayed as an endless resource for producing healthy cells that could be used for clinical application. Also, in other respects, iPS cells compared favorably to other cells, as they occur in humans naturally (Nishikawa et al. 2008). The only problem – already on the way to being solved – was their tendency to produce teratomas, and the use of a viral vector. Using fewer and other genetic factors and finding an alternative to viral vectors were to solve these problems.

Much was made of Yamanaka as the “good” scientist, who persevered in his quest to generate new medicines, spinning out Yamanaka's narrative that once it had occurred to him that the embryo he saw in a friend's lab through a microscope could have been like one of his daughters (interview 6 May 2006). When there was talk of the clinical application of iPS cells, the press quoted Yamanaka as saying that the simplicity of iPS cells warranted regulation, as in the near future anyone would be able to create them, including iPS cells that could be developed into gametes (Alford 2008, Anon 2008). The speed with which government support was mobilized for the new scientific discovery was unprecedented (interview Sato 17 March 2008). Prime Minister Fukuda, then the chair of the Cabinet's Council for Science and Technology Policy (CSTP, Kagaku Sogo Kenkyukai), ordered an urgent policy review, and MEXT immediately started developing policies to regulate iPS cell research and its future applications. Meetings with civil servants and scientists were promptly organized the month after Yamanaka and Takahashi's article was published in Cell, and by 22 December 2007 MEXT had made plans to raise the funding on iPS cell research from 270 million yen (US$2.5 million) for research in 2007, to 2.2 billion yen for the 2008 fiscal year, pledging 10 billion yen over the next five years (Cyranoski 2008). Half of the 2.2 billion yen was to be pumped into Yamanaka's iPS cell research to be housed in a new institute for iPS cell research at Kyoto University in the new national center, the Institute for Integrated Cell-Material Sciences (iCeMS). Furthermore, the MoHLW would channel close to 100 million yen in the 2008 fiscal year directly to Dr Yamanaka, in addition to 410 million yen for regenerative medicine infrastructure, such as a cell-processing center (Cyranoski 2008).

This move was made not just because research on pluripotency was no longer to be obstructed by bioethical hurdles, but also because many scientists, including Nakauchi Hiromitsu, Chairman of the Japanese Society for Regenerative Medicine (JSRM), pointed out that other countries could win the competition for medical applications and patents (see http://www.jsrm.jp/index.html). This concern was expressed in the regulation of the Japan Science and Technology Agency, which emphasized the need for paying attention to competition, the nature of patent acquisition and bioethical appropriateness (JSTA 2009).

But the majority of interviewed scientists in various fields of SCR (30 = 75%), when asked for their view on current policies on the allocation of science resources, doubted the wisdom of the government's heavy investment in iPS cell research. They argued that if one wants to cure diseases such as Alzheimer's or Parkinson's, a “rational” approach requires one to try out various possibilities: using different methods and different cells, comparing the success rates of fetal cells, hESR through SCNT and iPS cells. At present, they argue, it is not yet clear if any cell therapy works. And, if it does, it is not known which is most effective, and which is safest. However, the situation in Japan was not conducive to such a diversified approach.

Regulatory ambiguity: between permissiveness and ethicality

The disagreement in Japan about priorities in regenerative medicine is apparent in the development of bioethical regulation. An officially permissive approach permitted hESR to conduct research aiming to cure serious diseases, guiding the creation of hES cell lines and “special embryos” (toku teihai), while the urgency of regulating “therapeutic cloning” and iPS cell research to advancing research was recognized. But this permissive attitude was overshadowed by a bureaucratic approach to hESR. Complex procedures for both establishing ES cell lines and their use involving double-review by the institutional review board (IRB) and MEXT could take over a year (Nakatsuji 2007), while changes in protocol or research team required additional applications. Special equipment was required for storing and discarding hES cells, e.g. a furnace, and a room exclusively used for hES cells. Thus hES cell lines could not be stored in the same room as animal cells, even though they were maintained by animal (mouse) feeder. Ordinary hES cells then are to be respected, while their supposedly identical iPS cell counterparts did not receive any such treatment. Thus, the permissive approach aimed at advancing hESR was countered by a purist approach adopted by the regulatory bureaucracy, whose accountability for ethical research makes it responsible for improprieties and scandal.

The bureaucratic approach is informed by a circumspective attitude towards propriety. According to cell banker Murakami, civil servants run the risk of losing their jobs or of being sued if they are seen to be inappropriately backing fetal stem cell research or gene therapy, or allowing hESR without the utmost scrutiny. Gene therapy trials in Japan, according to fetal scientist Kawahara, are usually only attempted when American and European research has shown it is “safe.” Guidelines issued in the spring of 2006 stipulated that oocyte donation informed-consent procedures are only put in place when primate somatic cell nuclear transfer (SCNT) has been shown to be possible, or when human SCNT has succeeded abroad. These conditions took into account the increasingly louder views of feminist and disabled movements who stand up for the position of women; and took into account paternalistic attitudes associated with Japanese doctors and a growing distrust among the public of scientists' “Western” and “rational” approaches towards medicine, which are blamed for losing the “Japanese” human factor essential to a society plagued by suicides and an increase in “un-Japanese” practices such as using “brain death” as a criterion for pronouncing death, “euthanasia” and prenatal testing (Morioka 1995, Lock 2002, Tsuge 2010).

Ethical, reckless and scientific research

This section shows how the distinction between ethical, reckless and scientific research facilitates the understanding of Japan's policy turnaround in 2007–2008. Reliance on compromises between permissive and purist approaches created friction among policymakers, scientists and social movements, which was lessened by the discovery of iPS cells. The enormous attention given to iPS cells in late 2007 resulted from the relief of not having to deal with the thorny bioethical issues around embryo research in a field in which Japan had taken the global lead. The media speculated on the possibilities of using iPS cells in regenerative therapies without the problems of immune reaction and ethical dilemmas associated with oocyte and embryo donation. In December 2007, it was decided to invest substantially in iPS cells development and therapies, mainly institutionalized in the Center for iPS Cell Research and Application (CiRa) and the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University, and to speed up the development of iPS cells and patent law concentrated in Kyoto. At the beginning of 2008, the creation of so-called “Suupaa Tokku” – special research fields, such as for iPS cell research and hESR, organized around licensed research institutions – was designed to speed up the review of research proposals and the development of protocol (see Kitagawa and Woolgar 2008). A special task force from MEXT allowed therapeutic cloning in December 2007 (MEXT 2008), and in October 2008 various scientists expressed the belief that rules regarding oocyte donation would become less stringent in the near future (regulated in MEXT 2009). In October 2008, it was decided to loosen regulation around the application for hES cell lines (regulated in MEXT 2009),3 and in November 2008 the ethics committee of the CSTS allowed the creation of gametes from pluripotent cells.

Contrary to expectations, the majority of interviewed scientists regarded as “reckless” (musekinin) the radical switch in research emphasis from a purist and strictly regulated hESR regime to a bioethically correct but unregulated iPS cell research regime in late 2007.4 Pluripotent cells created from iPS cells were presented as identical to hES cells, even though scientists in Japan and in the USA commented on the limited available knowledge about the molecular processes underlying the reprogramming of somatic cells involving iPS cells. Nor had iPS cells been directed to differentiate into specific functional tissues or organs. And although alternatives to the use of teratoma-generating retroviruses were being sought, the introduction of genetic factors still meant that genetic alteration could take place, the consequences of which were hard to gauge. Thus, there was not yet confirmation of a genetic identity between the cell type generated from iPS cells and that of the patient. And, according to all interviewed stem cell scientists, the behavior of iPS cells and their therapeutic effectiveness depends on the environment in which the cells are going to end up. Concentrating on iPS cell research at the expense of other branches of SCR, according to most scientists, was a risky strategy: it threatened the loss of current expertise and it was based on unexplored presumptions about the nature of iPS cells.

Discussion

Bioethical regulation of hESR in the UK has been cited as rooted in public opinion, exemplified by the engagement of the public in debates on embryo and oocyte donation (Human Fertilisation and Embryology Authority: http://www.hfea.gov.uk/consultations/index.jsp). Developments in the Japanese governance of hESR show how regulation can be rooted in society differently. Although its public engagement strategy received little public response (Kato 2005), Japan's stem cell regulation was nevertheless largely steered by society. For, although the state adopted a permissive political stance towards hESR, its regulatory practice largely relied on the opinions of particular social groups. In accordance with Douglas' notion of “group,” public communication and views on regulation were influenced by natural symbols linked to danger rather than based on risk calculations. Japan's regulation and its implementation in the case of hESR was conditioned by a fear of scandal, while popular opinion was led by symbolic notions of what counts as “natural” reproduction and personal care in the context of the family. Thus, most of those in favor of oocyte and embryo donation described it in terms of helping a family member rather than as something that can be done on a large scale for public purpose (such as blood donation) or something that can become part of a commercial economy to help the ageing. IPS cell research on the other hand became associated with the possibility of wide commercial distribution and large-scale application in regenerative medicine. In 2008 there was little sign that iPS cell research would receive the same scrutiny as that to which hESR had been subject. Even though the adherence to existing ethical research regulation may formally determine whether science research is ethical, the mode of its creation and implementation was influenced by the societal environment. In Japan, hESR regulation was influenced through group symbols of ethicality, while their absence in the case of iPS cell research made it relatively insensitive to questions of risk in a similar research field. The resultant “recklessness,” a majority of interviewed stem cell researchers found equally damaging to scientific advancement.

Notes

In fact, extensive debate has been held on other bioethical topics, such as euthanasia, eugenics and surrogacy.

Similar views were obtained by Tsuge (2008); also see Lock (1998).

MEXT revised its guidance for human ES cells research (effective from 21 August 2009) by omitting the review by MEXT and easing the regulation for transferring cells created from human ES cells among research institutions (see http://ukinjapan.fco.gov.uk/resources/en/pdf/5606773/200908news).

Even the wider public in support of iPS cell research desired international regulation and restraint (Shineha et al. 2010).