Asian Bioethics Review

, Volume 9, Issue 3, pp 211–228 | Cite as

A Preliminary Study Exploring Japanese Public Attitudes Toward the Creation and Utilization of Human-Animal Chimeras: a New Perspective on Animals Containing “Human Material” (ACHM)

  • Mayumi Kusunose
  • Yusuke Inoue
  • Ayako Kamisato
  • Kaori Muto
Original Paper

Abstract

Ongoing research on making “human-animal chimeras” or “animals containing human material” (ACHM) to solve the shortage of organs available for transplantation has raised many ethical issues regarding the creation and utilization of such constructs, including cultural views regarding the status of those creations. A pilot study was conducted to explore Japanese public attitudes toward human-animal chimeras or ACHM. The February 2012 study consisted of focus group interviews (FGIs) with citizens from the Greater Tokyo Area, aged between 20 and 54. The 24 participants were divided into four groups. Transcripts of the interviews were analyzed and participants’ attitudes categorized. Five categories of participant attitudes were identified: (1) resistance to the unnatural, (2) concerns about animal welfare, (3) concerns about controlling human-animal chimeras, (4) concerns about the possible birth of intermediate entities, and (5) resistance to creating and utilizing animals containing my material or my child’s material. Our FGI results showed a broader and greater variety of public concerns than those reported in previous studies. While researchers have tried to establish new methods to avoid creating intermediate entities, our participants expressed concerns about not only intermediate entities but also animals containing their own material or their child’s material. Based upon their responses in the interviews, we are introducing a new ethical concern: “animals containing my material/my child’s material.”

Keywords

Human-animal chimeras ACHM Japanese public attitudes Focus group interviews Qualitative research 

Background

Regenerative research addressing the chronic shortage of organs available for transplantation is continually evolving. One area receiving increasing attention is the use of stem cell manipulation, using human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) to foster recovery of patients’ damaged or lost functions. One approach being studied is to create three-dimensional organs derived from a patient’s iPSCs in animal bodies: the creation of “human-animal chimeras.” The creation and utilization of such constructs have raised various ethical and societal concerns. To help identify and address those issues, this paper discusses a pilot study conducted to explore Japanese public attitudes toward human-animal chimeras or ACHM and the possibility of using them for transplantation.

Terminology

This paper uses the following definitions for specific terminology. A “hybrid” is an offspring of two plants or animals of different species. A “chimera” is defined as an organism composed of two or more genetically different types of cells, tissues, or organs. An “intermediate entity” refers to human-animal chimeras that have an especially human-like composition or that exhibit very human-like behaviors.

Another term, “animals containing human material” (ACHM), has been used in several studies (notably Grant and Williams (2010), the Academy of Medical Sciences (2011), and Ipsos MORI (2010) to denote chimeras composed of cells, tissues, or organs containing human genetic material in addition to cells, tissues, and organs containing genetic material from their own species. We follow those researchers and use ACHM to describe the chimeras in our study.

Current Status of Research on Human-Animal Chimeras

“Blastocyst complementation” is one of the techniques to create patient-derived organs in animal bodies. Pioneered by Hiromitsu Nakauchi, the technique entails creating, via genetic manipulation, pig blastocysts that lack the capacity to produce a certain organ. Human iPSCs are inserted into the blastocyst to create chimeric embryos. The chimeric embryos are then implanted in the pig’s uterus to be born as offspring with a human organ instead of the pig’s organ (Rashid et al. 2014).

If the process is successful, the new organs might be suitable for transplantation into human patients. The technique offers the possibility of developing patient-derived organs having less risk of rejection, and overcoming shortfalls in organ availability (Normile 2013; Shaw et al. 2015).

Currently, Nakauchi and his team have successfully created rat-mouse/mouse-rat chimeras that accept the other species’ iPS-derived organs (Kobayashi et al. 2010; Usui et al. 2012). They were also successful in producing organ-deficient pigs and allogeneic chimeric pigs (pig-pig chimeras), which they created large quantities (Matsunari et al. 2013). Furthermore, they successfully cured diabetic model mice by transplanting the insulin-producing cells of rat-grown pancreases (Yamaguchi et al. 2017). Juan Carlos Izpisua Belmonte and his team successfully made human-pig chimeric embryos in 2017 (Wu et al. 2017).

Ethical, Legal, and Social Issues on Human-Animal Chimeras

As human-animal chimera research became a real possibility, ethical, legal, and social issues that were entailed have generated much discussion in the scholarly literature. Issues such as the moral status of human-animal chimera (Fiesta and Düwell 2009; Nuyen and Bioethics Advisory Committee 2010; Deutscher Ethikrat 2011; Savulescu 2011), boundaries and moral confusion (Robert and Baylis 2003; Karpowicz et al. 2004, 2005; Deutscher Ethikrat 2011; Palacios-González 2015a; Shaw et al. 2015), humanization of chimeric animals (Greely 2011; Deutscher Ethikrat 2011; Palacios-González 2015b; Shaw et al. 2015; Bourret et al. 2016), violation of the natural order or playing God (Cobbe 2007; Nuyen and Bioethics Advisory Committee 2010; Deutscher Ethikrat 2011; Savulescu 2011), and moral humanization (Hyun 2015, 2016) have generated much discussion. Likewise, concerns about unknown infectious disease (Hug 2009; Nuyen and Bioethics Advisory Committee 2010; Shaw et al. 2015), animal welfare (Fiesta and Düwell 2009; Hyun 2015; Shaw et al. 2015; Bourret et al. 2016; Hyun 2016), human exceptionalism (Fox 2016), somatechnics (Mackenzie 2016), and arguments based on emotions or intuitions such as “wisdom of repugnance” (Kass 1997) and the “yuck factor”(Kass 1997; Midgley 2000; Nuyen and Bioethics Advisory Committee 2010; Mills 2014) have similarly drawn much attention.

Research studies have also increased, including studies on the public’s perception of this groundbreaking technology. Wilsdon and Willis (2004) examined how scientists and policy makers tended to focus on a framework of risk assessment for their discussions, without consideration of the importance of incorporating public voices and addressing public concerns regarding the need for such technology, who controls the process, and how it may affect patients and their families (Wilsdon and Willis 2004, pp. 28–29). Similarly, Marris and Rose (2010) argued the importance of recognizing “social factors,” such as beliefs, values, and assumptions, in consideration of shaping and funding research priorities. Other studies done by Ormandy and Schuppli (2014), Hug (2009), and Shaw et al. (2015) identified the importance of engaging with all the stakeholders including the public in order to gain support for controversial scientific research.

Why Conduct Qualitative Research on Public Attitude Toward Human-Animal Chimeras in Japan

There have been several qualitative studies sponsored by countries other than Japan. Different groups in New Zealand have conducted qualitative research on public attitude on introducing human genes into other organisms. Toi te Taiao: Bioethics Council (2004), NFO New Zealand (2003), and Mixed Media Limited of New Zealand (2004) found that participants’ perceptions were influenced by their fear of the unknown, loss of control, loss of choice, absence of need, ethical or moral concerns, interfering with the natural order, and concern for animals. They viewed ACHM as unnatural and against the spiritual aspects of nature and worried that such research was not adequately monitored.

Another significant qualitative study on public attitudes regarding ACHM was conducted by a team led by Ipsos MORI in the UK (Ipsos MORI 2010). Study results indicated that participants found the focus group discussion sessions educational. In general, many participants became supportive of ACHM research following the sessions, believing it was for the greater good. They wondered about what ethical or legal limits should be placed on such research. Participants also expressed interest in the economic effects of the research and were leery of research and treatments being controlled by large corporations and/or the wealthy. However, they were confident that governmental regulations would effectively address their apprehensions.

In Japan, two quantitative studies have been conducted on human-animal chimera research. Inoue et al. found that about 50% of Japanese citizens were against research that entailed the creation of human-animal chimeras, while a majority of researchers approved of such studies (Inoue et al. 2016). These results contrasted with a 2016 quantitative study assessing public attitude toward creating human-pig chimeras using blastocyst complementation which found 60% of respondents favored such research (Sawai et al. 2017).

While quantitative research is important, its key limitation is that participants’ responses are typically restricted to scales or “yes/no” answers. Ormandy and Schuppli (2014) stressed the importance of qualitative research, arguing that “[w]hen restricted response options do not allow for consideration of what people’s concerns are (e.g., why they might be opposed to certain types of research), it is difficult for policy makers to understand the nuance in attitudes in order to make progress in addressing societal concerns” (Ormandy and Schuppli 2014).

A qualitative approach to researching public perceptions on ACHM had not been conducted in Japan. Our research and analysis will help to clarify the public’s expectations and concerns regarding this technology and provide basic data for future discussions and research.

Methodology

Our pilot study consisted of focus group interviews (FGIs) conducted with citizens from the Greater Tokyo Area. The study design was adapted from the survey/ FGI methodology employed in Ipsos MORI’s 2010 study of public attitudes regarding ACHM in the UK. MORI’s study focused on the same topic and issues as ours and offered the opportunity to compare our results with MORI’s more comprehensive study.

FGIs are a well-established method for exploring the views of individuals in a group setting. The group setting of FGI encourages communication through the dynamic interaction of the group members, which can be advantageous in helping participants formulate opinions on unfamiliar topics, unlike the personal interviews (Kitzinger 1994). FGIs have been used to explore people’s expectations and risk perceptions of new technologies in many studies on genetic modification topics; genetic screening or carrier testing for particular disorders (McClaren et al. 2008; Schmidt et al. 2012); usage and treatment of embryos (Porter and Bhattacharya 2005; Ehrich et al. 2008; Roberts et al. 2010), and stem cell research (Ehrich et al. 2010; Illes et al. 2011; Eijkholt et al. 2012).

The protocol of this research was approved by the institutional review board at the Institute of Medical Sciences, The University of Tokyo (approval number: 23-63-0223, date of approval: February 23, 2012).

Our study consisted of 24 citizens of the Greater Tokyo selected from a preliminary survey measuring attitudes toward ACHM. In order to explore attitudes of wider community in the Greater Tokyo Area, people exhibiting a strong connection with animals, religion, or medicine were excluded from the final list of participants. The participants consisted of six males and six females in their 20s and 30s, and six males and six females in their 40s and 50s. Participants were divided into four focus groups consisting of a single sex and age range (Table 1). Each focus group was interviewed in 2-h sessions held in Tokyo on February 25 and 26, 2012.
Table 1

Participants’ characteristics

Group A

A-1

A-2

A-3

A-4

A-5

A-6

 Sex

Female

Female

Female

Female

Female

Female

 Age

29

28

28

37

30

37

 Marital status

Single

Single

Single

Married

Married

Married

 Occupation/industry

Law

Manufacture

Real estate

Housewife

Housewife

Education

Group B

B-1

B-2

B-3

B-4

B-5

B-6

 Sex

Male

Male

Male

Male

Male

Male

 Age

41

48

42

57

47

53

 Marital status

Single

Married

Married

Single

Single

Married

 Occupation/industry

Auto manufacture

Electronic manufacture

Hospital industry

Finance/insurance

Real estate

Auto manufacture

Group C

C-1

C-2

C-3

C-4

C-5

C-6

 Sex

Female

Female

Female

Female

Female

Female

 Age

40

45

47

51

52

54

 Marital status

Married

Married

Married

Married

Married

Single

 Occupation/industry

Housewife

Housewife

Hospitality industry (temporary)

Real estate (self-employed)

Housewife

Distribution sales (part-time)

Group D

D-1

D-2

D-3

D-4

D-5

D-6

 Sex

Male

Male

Male

Male

Male

Male

 Age

28

27

20

38

39

39

 Marital status

Single

Single

Single

Married

Married

Single

 Occupation/industry

Real estate

Student

Student

Public office/foundation/incorporated association

Manufacture

Software development/SI/multimedia contents development

Total: 24

Before the interviews, we prepared an interview guide and 40 flip boards containing pictures and illustrations of fundamental information corresponding to the discussion topics. A professional facilitator was made available to respond to questions about the scientific aspects of the topic.

In our FGIs, the participants were asked to answer and discuss sequentially the following questions:
  1. (1)

    Degree of familiarity with chimeras and chimera studies

     
  2. (2)

    Attitude about the use of animals as research subjects

     
  3. (3)

    Attitude about implanting animal materials into humans (and more specifically, the research participants and their families)

     
  4. (4)

    Attitude about producing and utilizing individual animals for the purpose of resolving organ shortages

     
  5. (5)

    Animal species that would be acceptable to be produced and utilized for medical purposes

     
  6. (6)

    Organs that would be acceptable for regeneration within animal bodies and utilization for medical purposes

     
  7. (7)

    Degree of familiarity with current regulations regarding chimera studies in regenerative medicine

     

Unlike MORI’s study, in which UK participants received information on ACHM prior to the FGIs, Japanese participants received less information on chimeras before the interviews because one of our goals was to observe the initial reactions and honest feedback of the participants.

To analyze the data, we adopted thematic analysis (Boyatzis 1998; Guest et al. 2012). Interviews were audio recoded and transcribed verbatim. Then the data was sifted, thematically sorted, and analyzed. We carefully considered the actual words used and their meanings, context, frequency, intensity, specification of responses, internal consistency, big ideas, and the participants’ perceptions of importance. Following this initial analysis, the segments identified as meaningful information were extracted and categorized. Once all the group interview data had been processed, the categories were compared and organized. At the stage of final analysis, a chart was created to compare all the items and categories, which were then rearranged into appropriate thematic groups.

In the following sections of this paper, we will mainly discuss the findings regarding “attitudes about producing and utilizing individual animals for the purpose of resolving organ shortages.” This was the primary rationale for conducting the pilot study and is one of the internationally discussed issues that may trigger regulatory changes in this field and possibly profoundly affect the relationship between humans and animals in both the biomedical and societal contexts. Our findings, though preliminary, offer new information regarding perceptions regarding human-animal chimeras.

Results

Most participants did not have any knowledge about studies on the creation of human organs inside animal bodies. However, in conjunction with utilizing information provided by the facilitator, they shared relevant information that they thought they had acquired through newspapers, TV, comics, and science fiction animation and movies to discuss the topics.

Our results identified four thematic groups for the topic of “attitudes about producing and utilizing individual animals for the purpose of resolving organ shortages”: (1) resistance to the unnatural, (2) concerns about animal welfare, (3) concerns about controlling human-animal chimeras, (4) concerns about the possible birth of intermediate entities, and (5) resistance to creating and utilizing animals containing my material/my child’s material. Participants’ responses included in the discussion have been translated by the authors into English from Japanese.

Resistance to the Unnatural

Most participants in our FGIs had a tendency to value “nature.” They considered nature in itself to be good. Manipulation of natural objects was unacceptable to most participants. Some expressed strong resistance to the creation and utilization of human-animal chimeras, because these entities would not include natural features that distinguish them from ordinary animals. In particular, they viewed the creation and then killing of unnatural entities solely for transplantation purposes as unnecessary.

Well, though it might be safer to use organs consisting of human cells… In the case of a baboon, a natural-born baboon was killed so that its heart could be transplanted; but in this [human-]pig [chimera]’s case, humans would artificially create an organ-deficient pig on purpose, and manage it so that it is born; what is more, a pig would be implanted with human cells, and then the pig’s heart would be taken out for human’s preferences; consequently, the pig would die because it lost its own heart. I feel the pig was forcibly created for my own sake. (Female in her 20s)

One of her concerns was that manipulating the birth and death of human-animal chimeras went against the natural order for the sake of only one single person.

If the human-like creatures, such as human-pig chimeras as previously shown, were created, I am not sure it would be a good thing to create them only for organs. I don’t think I would receive a transplant; instead, I think I would just accept my natural life. I guess it is the same reason that the number of transplants does not increase. I believe it is good to let nature take its course. Well, it is okay to extend life with an operation or something, but I believe it is not necessary to try it [to create chimeric animals] forcibly by destroying natural entities. (Female in her 40s)

Other participants shared this women’s view of using nature as the criterion of the acceptability of death. For them, a natural death was better than a longer life achieved through the use of life-prolonging procedures, including organ transplantation, especially if it involved the creation of chimeras.

Similarly, some participants expressed the opinion that manipulation of natural objects might cause harm to human beings. These sentiments were derived not only from the negative attitude toward the violation of the natural order but also from an anxiety arising from safety issues. Most participants displayed a cautious attitude toward genetically modified materials because there was no guarantee about the long-term safety of intake of genetically modified substances. They believed that the consumption of natural materials guaranteed long-term safety of the human body.

Overall, Japanese participants valued what they perceived as a natural order and considered nature to play a significant role in their judgments and decisions.

Concerns About Animal Welfare

Some participants felt compassion and pity for chimeric animals that were modified and manipulated although they acknowledged the necessity of animal experimentation for medical developments.

I feel pity for animals that are genetically manipulated, though I understand the experiments are important. (Female in her 20s)

Other participants expressed concern about the vulnerability of animals being exploited.

… It is because ‘buta-san’ [‘the piggy’ or ‘Mr. Pig’] could not create its own heart from the beginning that human cells would be implanted. What is more, gene modification would be employed to produce ‘buta-san’ without a heart. I am very concerned about those things. I feel pity. (Female in her 20s)

In her perspective, organ deficit pigs are being deprived of their own organs and since they cannot create their own organs, they were made to rely on human cells and human intervention to survive. This remark provided insights into how entities in research were viewed as vulnerable, as well as a less anthropocentric perspective.

Interestingly, participants called human-pig chimera as “buta” at the beginning of the interview, but as the discussion progressed, the participants began to call it “buta-san.” In Japanese, “buta” means “pig” and “-san” is a suffix to be added after a noun to reference the subject with politeness. Regardless of age and sex, the Japanese participants tended to describe pigs with a suffix as “buta-san” (“Mr. Pig” or piggy), when they talked about sacrificing pigs in research. This may be anthropomorphizing their feelings onto the pig, or it could be recognition of the pigs as living creatures rather than “objects.”

Concerns About Controlling Human-Animal Chimeras

Many participants expressed concerns about the impact that creating and utilizing human-animal chimera would have on humans. They wondered about what could happen if humans became unable to control them. They worried that the human-animal chimera might jeopardize humans and their natural environment if they escaped.

… Make sure to get [human-animal chimeras] controlled. Talking about control might sound extremely ambiguous, but let’s say such odd pigs are born and destroy the ecosystem, we would be stumped… (Male in his 50s)

I am not sure whether it is good for mankind to try their hands in such a field [creating chimeras] or whether they can handle it. I feel that it might lead us beyond repair if mankind became unable to control the chimeric animals. I am afraid that mutant or new organisms which mankind could not control might be born. (Male in his 30s)

Another participant criticized the idea that human-animal chimeras should be exterminated when they escaped, describing that view as human egoism.

Imagine researchers creating chimeras, the chimeras proliferate and escape, escaped chimeras proliferate again, and then humans exterminate the chimeras. [If those things happened,] I think it is nothing but [humans’] egoism. (Male in his 40s)

Concerns About the Possible Birth of Intermediate Entities

Participants expressed concerns about the possible birth of intermediate entities, their ethical rights, and questioned the boundaries between humans and animals.

The closer [to humans the animals become], the more suitable for transplant they would be; but when animals get closer and closer to human beings, it leads to a boundary issue whether they should be considered as humans or animals. (Female in her 50s)

… I wonder how people or countries that supported the experiments would take responsibility if an intermediate entity were to be born, generated his own consciousness, and doubted his own existence. The chances of such a case might be very slim; but due to human errors, I don’t think it could never happen. I do believe there is some probability that a therianthrope or human-pig chimera might be created for real. I feel a bit scared when I imagine him asserting his human rights even though he was similar to a pig. (Male in his 40s)

These participants raised concerns about the social status of intermediate entities with a human-like appearance or with self-consciousness. Others expressed concerns over whether we should provide some form of human rights to these intermediate entities, and who would take responsibility for them if they were born.

Resistance to Creating and Utilizing Animals Containing My Material/My Child’s Material

Some participants showed strong concerns about utilizing human-animal chimeras that contained their own genetic material, or their child’s genetic material. Mothers showed especially strong feelings about the creation of animals that included their own child’s material; they tended to manifest concerns about not only using the human-animal chimera but also creating them. They viewed such creatures as having a special status. The presence of their own or their child’s genetic material made the chimera a relative. They had reservations about killing such chimeras.

In my case, as I said before, whatever animals they are, maybe I feel resistance in killing something that inherited my genes. (Male in his 20s)

As I said before, despite the shortage, I still feel resistance to create a creature that contains my cells and eventually kill it; in that case, I think it would rather be better to choose baboons for transplantation. Though I wonder what kind of animal would be born, it contains my cells, right? … Then, I don’t think I can. (Female in her 40s)

Many participants viewed human-animal chimeras containing the respondents’ own cells as family and compared their creation and use to using their own children for transplantation purposes, or “my child.”

Suppose the opposite situation, I mean putting a human in the pigs’ situation; in that situation my child is growing in mom’s belly; then I would be asked if I wanted to kill the child and have its heart transplanted. In other words, the only difference is that its mother is not a pig but a human. So I feel strong resistance. (Male in his 20s)

In the end, the piggy will be killed after organs are taken out of them. Eventually… Well, if it were not a pig but a human, it is surely the same as killing my own child. (Male in his 30s)

Participants also expressed concerns and opposition to creating ACHM that contain their own child’s genetic material.

I am against it. I cannot do such things with taking the risk of what kind of entity would be born. The pig that has my child’s cells eventually dies, doesn’t it? Even though I think it is on behalf of my child, I cannot insist on pursuing my ego no matter what happens. (Female in her 40s)

Even more, the entity that has my child’s cells would be created. That is the biggest problem. (Female in her 40s)

Perceiving the chimera with their genetic material as special or family, participants questioned and expressed concern about how the chimera’s body would be handled after it was used for transplant.

It is odd to think about how to treat the body after transplantation, but suppose it [the body] would be dealt with rudely or, I don’t think it could happen but, suppose it [the body] would be disposed of with other ordinary waste without mercy, and so on, I have mixed feelings. (Female in her 50s)

The notion that a dead human body ought to be treated with respect is strongly embedded in Japanese culture. It appears that the participants believe that a chimeric body should be treated with respect and dignity because it contained a human adult or child’s materials.

Discussion

Comparison Between the Japanese Participants’ Attitude and the UK’s Public Attitude

Comparing our results to those of MORI’s UK study, we find many differences and that may be based on cultural attitudes toward, as well as perceptions of, human-animal chimera.

We found three main differences in public attitudes. First, the Japanese participants in our study predominately opposed human-animal chimera research. The only exceptions were men in their 20s. Of special note, most Japanese participants replied negatively when they were asked whether they would accept an organ nurtured inside of a chimeric animal. This contrasts with UK FGI results where each group, regardless of age or sex, favored the creation of human organs in chimeric animals.

Second, a majority of UK participants wanted to know if fair and equitable distribution of the benefits from human-animal chimera research would be achieved (Ipsos MORI 2010, p. 5). Only one participant in our study raised that issue. Other participants were more concerned about the creation and nature of the chimeras.

Third, UK participants expressed greater trust in the adequate enforcement of regulations dealing with chimera research than participants in our study (Ipsos MORI 2010, p. 5). Our participants expressed skepticism about the effectiveness of the current Japanese regulatory system.

Both studies reveal a number of similarities in participant perceptions. Both study participants expected benefits from medical developments, but they worried about the possibility that ethically unacceptable studies would be approved if the initial human-animal chimera study was permitted, echoing the slippery slope argument (Hug 2009; Savulescu 2011). Though concerned about animal rights (Ipsos MORI 2010, pp. 4–5, pp. 34–36), all participants saw a fundamental difference in the rights of the chimeras compared to humans. They also worried about regulatory compliance and enforcement, fearing that human-animal chimeras might jeopardize humans and their natural environment if not adequately controlled, which has been framed as an ecological risk argument (Fiesta and Düwell 2009).

Overall, participants in both MORI’s UK study and our pilot study in Japan voiced similar responses to most of the FGI discussion items. The one item which yielded a clear cultural/perceptual difference was item (4), which relates to attitudes about producing and utilizing individual animals for the purpose of resolving organ shortages. In our study, participants expressed resistance to creating and utilizing animals containing either their own or their child’s genetic material. No similar outlook was detected in UK participants. This finding has important implications for ACHM research worldwide and for Japan in particular.

Japanese Participants’ Attitude Toward “Human-Animal Chimeras,” or “Animals Containing Human Material”

We identified five response groupings for our study’s findings on FGI item 4: attitudes about producing and utilizing individual animals for the purpose of resolving organ shortages. In an earlier section of this paper, we dealt in detail with each response grouping. Responses for the first four groupings were similar to those found in the other research studies mentioned earlier in this paper. However, the fifth issue “resistance to creating and utilizing animals containing my material/my child’s material” yielded comments that are so different from other study results that they reveal what may be considered a unique perspective inherent in research into producing organs inside animal bodies by employing autologous iPSC transplantation technologies.

New Perspective: Not Just “Animals Containing Human Material” but “Animals Containing My Material” (ACMM)

Participants in our study—regardless of age or sex—expressed particular perspectives and feelings toward chimeras containing their own cells or their child’s cells. During the FGI, we observed that how participants described human-pig chimeras changed from a pig or odd pigs to Mr. Pig/Piggy, a creature that contains my/my child’s cells, my/my child’s genes, or my child. It is noteworthy that the status participants in our FGIs initially gave to the human-animal chimeras changed from “the outsider,” “the hazardous entity,” and “the expendable animals” to “the entity that shared some parts with themselves” or “the entity whose existence had a special significance for them.” Ultimately, such human-animal chimeras were no longer just laboratory animals or expendable animals for medical use, but had morphed into an entity entitled to respect and a type of social status. The change in perception indicates a status change when participants’ own genetic material is used. Participants began to move beyond the personal connection to a societal/cultural one when discussing disposal of the chimera’s body.

In the Japanese culture, it is customary for people to keep their/their children’s body parts, such as umbilical cord, infant’s hair or teeth, as symbols or tokens of association or celebration of growth (NTT DATA 2017). Japanese people retain a relationship with departed friends or relatives through preserving body parts of their loved ones. Similar things can be seen in relationship between donors’ family and a recipient in organ transplant. We sometimes hear the family members of some organ donors say that their son or daughter is still living in the recipient’s body.

The perception concerning chimeras containing “my material” is dissimilar to the issues of chimeric animals with human-like external features discovered during pre-natal examination discussed by Bourret et al. (2016). In our study, the human features of chimera are derived from “my cells” or “my child’s cells” and do not entail any human-like external features. It is the donated cells, not external appearance, which creates the attachment between donor and chimera. It is the cell donor who has caused the pain and suffering endured by the animals containing their materials, especially when the donation is predicated on a creature being deprived of its natural organs, or results in the death of the chimera. Recognizing their role in the situation create, for many people, complex feelings of attachment, affection, and/or guilt toward the aborted human-animal chimera.

This relationship creates issues in other areas of ACHM research such as the pre-emptive production of multiple human-animal chimeras in case of need. If this was done, a decision would be required on how to deal with the redundant chimeras, the siblings of the life-saving chimera animal. The perceptions that our study has uncovered suggest that each redundant chimera would be considered as having a relation to its human donor and deserving of a status higher than a mere “object.” The psychological impact on donors must be considered when addressing ACHM concerns.

Beyond our study, the famous Henrietta Lacks story is another example of perceiving chimeras containing human genetic material as more than “objects.” In the Lacks story, Henrietta’s cells (HeLa cells) have been distributed globally for medical science advancement. For researchers, the HeLa cells are just cells or a tool that they can buy and use for their research. However, for Lacks’ family, the HeLa cells are not just cells or things but rather parts of Henrietta or “mother”; the family found special meaning in the cells and felt connected with the deceased individual (Skloot 2010). The lesson to be learned from the story behind the HeLa cells is that behind the scientific research that uses human materials, the perceptions of research participants, patients, and their families need to be taken into account.

While issues such as species, dignity, and moral status have been heavily discussed in the ACHM literature, little attention has been given to the perspective of “animals containing my material” or “animals containing my childs material,” related to association and attachment among cell donors, their family, and chimeric animals.

If researchers and policy makers consider public understanding as important, perceptions like those of our FGI participants must be considered when analyzing why people may oppose creating human-animal chimeras in research. Their views must be addressed and incorporated into the discussion, and not dismissed as just anthropomorphism.

“Interspecies Conceptus Complementation” and FGI Participants’ Concerns

Reflecting on the concerns raised regarding the ethical and social implications pertaining to the creation and utilization of human-animal chimeras, researchers have tried to establish new methods. For instance, some researchers proposed a new method, called “interspecies conceptus complementation,” as an alternative to blastocyst complementation. In this method, progenitor cells, instead of iPSCs, are injected into the targeted place of an embryo at the right time to ensure that human cells do not mix with animal nerve cells or germ cells (Kobayashi et al. 2014; Rashid et al. 2014).

It is true that the creation of intermediate entities is one of the principal public concerns, and the arduous efforts of researchers to avoid such an outcome should be acknowledged. However, the participants in our FGIs did not distinguish between chimeras and intermediate entities since both types of entities would contain their own material or their child’s material. Our results suggest that mere creation of chimeric animals with “my material” or “my child’s material” may invoke people’s anxiety. Furthermore, mixing animals with “my material” or “my child’s material” might also be one of the unpalatable factors, or so-called “yuck factors,” for some people. In this case, there are gaps between people’s concerns, as expressed in our FGIs, and researchers’ responses to address issues concerning the creation and utilization of human-animal chimeras.

In conclusion, our FGI results showed a broader and greater variety of public concerns than those reported in the previous studies. From the new perspective of “animals containing my material/my child’s material” that our study has unveiled, we suggest that it is important and necessary not only to consult with various experts, but also to incorporate a broad range of public perspectives by facilitating public dialog with all stakeholders, especially with patients and their families, regarding human-animal chimera research.

In this regard, Evans and Durant point out that the public need not necessarily agree with research that is tainted with ethical problems just because their knowledge of the research increases. They believe that it is not prudent for scientists and policy makers to expect that well-informed citizens would automatically support any and all scientific research (Evans and Durant 1995). It should be noted that gaining public understanding for human-animal chimera research by providing only scientific knowledge is not enough. Thus, we expect that the perspective derived from our FGI will help to fill in the understanding gap between researchers and the public.

In sum, we recommend that regulation and preventive safeguards be further considered through greater communication and explanation to address the concerns identified in our study. We also recommend that researchers and policy makers explain the status of regulation and compliance of researchers concerning human-animal research and how regulation has effectively prevented the situation that ordinary people are concerned about.

In response to concerns about animal welfare, it is important for researchers to practice, at least, the “three Rs” (replacement, reduction, and refinement). We also recommend that researchers explain the reasons for using animals in research; how human-animal chimeras, including redundant creations, are dealt with; and how to reduce the chimera’s pain and suffering, whether in the context of research or therapy.

Limitations of This Research

As mentioned, this research was conducted as a pilot study, and we recognize the limitations of our research. Firstly, being an exploratory study, our research needs further validation. Secondly, although we collected the data necessary to enable further research—through compiling the meaningful discussions held among the participants, our sample size is too small to generalize our findings. More specifically, our sample was limited to the Greater Tokyo Area. Moreover, our sample did not include individuals with strong views about medicine, religion, or animals. Therefore, we consider it important for future research to include the views of people who have experienced serious health problems, participants who are strongly religious, and those who consider animal welfare to be important.

Notes

Acknowledgements

We would like to thank the citizens who participated in the focus group interviews. We acknowledge the contributions and helpful suggestions of Professor Hyunsoo Hong and members of the Department of Public Policy at the University of Tokyo as well as Dr. Shimon Tashiro at the National Cancer Center for helpful suggestions. Additionally, the authors would like to express special gratitude to Professor Hocine Fetni at the University of Pennsylvania and Professor Robert Congleton of Rider University for editing the English paper and their valued advice.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

A Human Subjects’ Protection Statement

The protocol of this research was approved by the institutional review board (IRB) at the Institute of Medical Sciences, The University of Tokyo (approval number: 23-63-0223, date of approval: February 23, 2012).

References

  1. Academy of Medical Sciences. 2011. Animals containing human material. United Kingdom: The Academy of Medical Sciences. Available at www.acmedsci.ac.uk/download.php?file=/images/project/Animalsc.pdf. Accessed 11 May 2016.
  2. Bourret, R., Martinez, E., Vialla, F., Giquel, C., Thonnat-Marin, A., and De Vos, J. 2016. Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs. Stem Cell Research & Therapy 7(1): 87.Google Scholar
  3. Boyatzis, R.E. 1998. Transforming qualitative information: thematic analysis and code development. The United States of America: Sage Publishing.Google Scholar
  4. Cobbe, N. 2007. Cross species chimeras: exploring a possible Christian perspective. Zygon 42 (3): 599–628.CrossRefGoogle Scholar
  5. Deutscher Ethikrat. 2011. Human-animal mixtures in research: opinion. Germany: The German Ethics Council. September 27. Available at http://www.ethikrat.org/files/opinion-human-animal-mixtures-in-research.pdf. Accessed 5 July 2016.
  6. Ehrich, K., Williams, C., and Farsides, B. 2008. The embryo as moral work object: PGD/IVF staff views and experiences. Sociology of Health & Illness 30(5): 772–787.CrossRefGoogle Scholar
  7. Ehrich, K., Williams, C., and Farsides, B. 2010. Fresh or frozen? Classifying ‘spare’ embryos for donation to human embryonic stem cell research. Social Science & Medicine 71(12): 2204–2211.CrossRefGoogle Scholar
  8. Eijkholt, M., Kwon, B., Mizgalewicz, A., and Illes, J. 2012. Decision-making in stem cell trials for spinal cord injury: the role of networks and peers. Regenerative Medicine 7(4): 513–522.Google Scholar
  9. Evans, G., and Durant, J. 1995. The relationship between knowledge and attitudes in the public understanding of science in Britain. Public Understanding of Science 4(1): 57–74.Google Scholar
  10. Fiesta, A., and Düwell, M. 2009. IV. Ethics—ethical issues raised by chimera and hybrids—an overview. In CHIMBRIDS−Chimeras and Hybrids in Comparative European and International Research− Scientific, Ethical Philosophical and Legal Aspects, eds. J. Taupitz and M. Weschka, 61–77. Berlin: Springer.Google Scholar
  11. Fox, M. 2016. What is special about the human body? Law, Innovation and Technology 7: 206–230.CrossRefGoogle Scholar
  12. Grant, L. and Williams, B. 2010. Exploring the boundaries: a dialogue on animals containing human material: evaluation report. United Kingdom: Laura Grant Associates. Available at http://www.acmedsci.ac.uk/policy/policy-projects/animals-containing-human-material/. Accessed 11 May 2016.
  13. Greely, H. T. 2011. Human/nonhuman chimeras: assessing the issues. Beauchamp, T. L. and Frey, R. G. (Eds.). The oxford handbook of animal ethics. Oxford University Press. pp. 641–670. Available at http://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780195371963.001.0001/oxfordhb-9780195371963-e-25. Accessed 20 April 2017.
  14. Guest, G., MacQueen, K.M., and Namey, E.E. 2011. Applied thematic analysis. The United States of America: Sage Publishing.Google Scholar
  15. Hug, K. 2009. Research on human-animal entities: ethical and regulatory aspects in Europe. Stem Cell Reviews 5: 181–194.CrossRefGoogle Scholar
  16. Hyun, I. 2015. From naive pluripotency to chimeras: a new ethical challenge? Development 142: 6–8.CrossRefGoogle Scholar
  17. Hyun, I. 2016. What’s wrong with human/nonhuman chimera research? PLoS Biology 14: e1002535.CrossRefGoogle Scholar
  18. Illes, J., Reimer, J.C. and Kwon, B.K. 2011. Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition. Stem Cell Reviews and Reports 7(4): 997–1005.Google Scholar
  19. Inoue, Y., Shineha, R., and Yashiro, Y. 2016. Current public support for human-animal chimera research in Japan is limited, despite high levels of scientific approval. Cell Stem Cell 19(2): 152–153.Google Scholar
  20. Ipsos MORI. 2010. Exploring the boundaries: report on a public dialogue into animals containing human material. United Kingdom: Academy of Medical Science. Available at http://www.ipsos-mori.com/researchpublications/publications/1377/Exploring-the-Boundaries.aspx. Accessed 11 May 2016.
  21. Karpowicz, P., Cohen, C.B., and Van der Kooy, D. 2004. It is ethical to transplant human stem cells into nonhuman embryos. Nature Medicine 10(4): 331–335.CrossRefGoogle Scholar
  22. Karpowicz, P., Cohen, C.B., and Van der Kooy, D. 2005. Developing human-nonhuman chimeras in human stem cell research: ethical issues and boundaries. In CHIMBRIDS−Chimeras and Hybrids in Comparative European and International Research− Scientific, Ethical, Philosophical and Legal Aspects, eds. J. Taupitz and M. Weschka, 535–555. Berlin: Springer.Google Scholar
  23. Kass, L.R. 1997. The wisdom of repugnance: why we should ban the cloning of humans. New Republic 216: 17–26.Google Scholar
  24. Kitzinger, J. 1994. The methodology of focus groups—the importance of interaction between research participants. Sociology of Health & Illness 16: 103–121.CrossRefGoogle Scholar
  25. Kobayashi, T., Yamaguchi, T., Hamanaka, S., Kato-Itoh, M., Yamazaki, Y., Ibata, M., Sato, H., Lee, Y.S., Usui J., Knisely, A.S., Hrabayashi, M., and Nakauchi, H. 2010. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell 142: 787–799 Available at http://www.sciencedirect.com/science/article/pii/S0092867410008433 Accessed 11 May 2016.
  26. Kobayashi, T., Kato-Itoh, M., and Nakauchi, H. 2014. Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation. Stem Cells and Development 24(2): 182–189.Google Scholar
  27. Mackenzie, R. 2016. Queering Spinoza’s somatecnics: stem cells, strategic sacralisations and fantasies of care and kind. In Somatechnics: queering the technologisation of bodies. Kindle ed, ed. S. Murray. New York: Taylor and Francis.Google Scholar
  28. Marris, C., and Rose, N. 2010. Open engagement: exploring public participation in the biosciences. PLoS Biology 8(11): e1000549.Google Scholar
  29. Matsunari, H., Nagashima, H., Watanabe, M., Umeyama, K., Nakano, K., Nagaya, M., Kobayashi, T., Yamaguchi, T., Sumazaki, R., Herzenberg, L. A., and Nakauchi, H. 2013. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proceedings of the National Academy of Sciences 110(12): 4557–4562 Available at http://www.pnas.org/content/early/2013/02/13/1222902110.abstract Accessed 11 May 2016.
  30. McClaren, B., Delatycki, M., Collins, V., Metcalfe, S., and Aitken, M. 2008. ‘It is not in my world’: an exploration of attitudes and influences associated with cystic fibrosis carrier screening. European Journal of Human Genetics 16(4): 435–444.Google Scholar
  31. Midgley, M. 2000. Biotechnology and monstrosity: why we should pay attention to the “yuk factor”. Hastings Center Report 30 (5): 7–15.CrossRefGoogle Scholar
  32. Mills, C. (2014) Commentary: In defence of repugnance. Akabayashi, A. (Ed.). The future of bioethics: international dialogues. Oxford University Press. pp. 366-370.Google Scholar
  33. Mixed Media Limited. 2004. Report to the bioethics council on the dialogue events focusing on human genes in other organisms. New Zealand: Mixed Media Limited. June 7. Available at http://ndhadeliver.natlib.govt.nz/delivery/DeliveryManagerServlet?dps_pid=IE27291715. Accessed 31 July 2017.
  34. NFO World Group: NFO New Zealand. 2003. Human genes in other organisms: qualitative research report - Prepared for: The Bioethics Council. Wellington, New Zealand: Toi te Taiao: Bioethics Council. August. Available at http://ndhadeliver.natlib.govt.nz/ArcAggregator/arcView/frameView/IE586117/http://www.bioethics.org.nz/. Accessed 14 May 2016.
  35. Normile, D. 2013. Chimeric embryos may soon get their day in the sun. Science 340 (6140): 1509–1510 Available at http://www.sciencemag.org/content/340/6140/1509.summary (accessed May 11, 2016).CrossRefGoogle Scholar
  36. NTT DATA Institute of Management Consulting, Inc. 2017. Social awareness survey on regenerative medicine: the key to donate human cells for regenerative medicine is adjusting the environment to donors’ preferences. Japan: NTT DATA institute of management consulting, Inc. (Japanese). Available at: http://www.keieiken.co.jp/aboutus/newsrelease/170307/ Accessed 1 Sep 2017.
  37. Nuyen, A. 2010. Stem cell research and interspecies fusion: some philosophical issues. Available at: http://www.bioethics-singapore.org/images/uploadfile/65151%20PMStem%20Cell%20Research%20And%20Interspecies%20Fusion.pdf Accessed 1 Sep 2017.
  38. Ormandy, E.H., and Schuppli, C.A. 2014. Public attitudes toward animal research: a review. Animals (Basel) 4: 391–408.Google Scholar
  39. Palacios-González, C. 2015a. Human dignity and the creation of human–nonhuman chimeras. Medicine, Health Care and Philosophy 18: 487–499.CrossRefGoogle Scholar
  40. Palacios-González, C. 2015b. Ethical aspects of creating human-nonhuman chimeras capable of human gamete production and human pregnancy. Monash Bioethics Review 33: 181–202.CrossRefGoogle Scholar
  41. Porter, M., and Bhattacharya, S. 2005. Investigation of staff and patients’ opinions of a proposed trial of elective single embryo transfer. Human Reproduction 20(9): 2523–2530.Google Scholar
  42. Rashid, T., Kobayashi, T., and Nakauchi, H. 2014. Revisiting the flight of Icarus: making human organs from PSCs with large animal chimeras. Cell Stem Cell 15: 406–409.Google Scholar
  43. Robert, J.S., and Baylis, F. 2003. Crossing species boundaries. American Journal of Bioethics 3(3): 1–13.Google Scholar
  44. Roberts, S.A., McGowan, L., Hirst, W. M., Brison, D.R., Vail, A., and Lieberman, B.A. 2010. Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives. Health Technology Assessment 14(38): 1–237.Google Scholar
  45. Savulescu, J. 2011. Genetically modified animals: should there be limits to engineering the animal kingdom?. In The Oxford Handbook of Animal Ethics, eds. T. L. Beauchamp and R. G. Frey, 641–670. New York: Oxford University Press. Available at http://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780195371963.001.0001/oxfordhb-9780195371963-e-24. Accessed 20 April 2017.
  46. Sawai, T., Hatta, T., and Fujita, M. 2017. Public attitudes in Japan towards human–animal chimeric embryo research using human induced pluripotent stem cells. Regenerative Medicine. 12: 233-248.Google Scholar
  47. Schmidt, J., Castellanos-Brown, K., Childress, S., Bonhomme, N., Oktay, J., Terry, S., Kyler, P., Davidoff, A., and Greene, C. 2012. The impact of false-positive newborn screening results on families: a qualitative study. Genetics in Medicine 14(1): 76–80.Google Scholar
  48. Shaw, D., Dondorp, W., Geijsen, N., and de Wert, G. 2015. Creating human organs in chimaera pigs: an ethical source of immunocompatible organs? Journal of Medical Ethics 41(12): 970–974.CrossRefGoogle Scholar
  49. Skloot, R. 2010. The immortal life of Henrietta Lacks. Reprint ed. New York: Crown.Google Scholar
  50. Toi te Taiao: Bioethics Council. 2004. The cultural, ethical and spiritual dimensions of the use of human genes in other organisms. Wellington, New Zealand: Bioethics Council. Available at http://ndhadeliver.natlib.govt.nz/ArcAggregator//arcView/resource/IE586117//http://www.bioethics.org.nz/publications/human-genes-final-report-aug04/cultural-ethical-and-spiritual-dimensions-of-human-genes-in-other-organisms.pdf. Accessed 14 May 2016.
  51. Usui, J., Kobayashi, T., Yamaguchi, T., Knisely, A. S., Nishinakamura, R., and Nakauchi, H. 2012. Generation of kidney from pluripotent stem cells via blastocyst complementation. The American Journal of Pathology 180(6): 2417–2426 Available at http://www.sciencedirect.com/science/article/pii/S0002944012002386# Accessed 11 May 2016.
  52. Wilsdon, J. and Willis, R. 2004. See-through science: why public engagement needs to move upstream. London: Demos. https://doi.org/10.13140/RG.2.1.3844.3681.
  53. Wu, J., Platero-Luengo, A., Sakurai, M., Sugawara, A., GiI, M.A., Yamaguchi, T., Suzuki, K., Bogliotti, Y.S., Cuello, C., Morales Valencia, M., Okumura, D., Luo, J., Vilarino, M., Parrilla, I., Soto, D.A., Martinez, C.A., Hishida, T., Sanchez-Bautista, S., Martinez-Martinez, M.L., Wang, H., Nohalez, A., Aizawa, E., Martinz-Ressondo, P., Ocampo, A., Reddy, P., Roca, J., Maga, E.A., Esteban, C.R., Berggen, W.T., Nunez Delicado, E., Lajara, J., Guillen, I., Guillen, P., Campistol, J.M., Martinez, E.A., Ross, P.J., and Izpiua Belmonte, J.C. 2017. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168: 473–486 e15. Available at http://www.cell.com/cell/pdf/S0092-8674(16)31752-4.pdf Accessed 20 April 2017.
  54. Yamaguchi, T., Sato, H., Kato-Itoh, M., Goto, T., Hara, H., Sanbo, M., Mizuno, N., Kobayashi, T., Yanagida, A., Umino, A., Ota, Y., Hamanaka, S., Masaki, H., Rashid, S.T., Hirabayashi, M., and Nakauchi, H. 2017. Interspecies organogenesis generates autologous functional islets. Nature 542: 191–196. Available at http://www.nature.com/nature/journal/v542/n7640/abs/nature21070.html?lang=en Accessed 20 April 2017.

Copyright information

© National University of Singapore and Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Mayumi Kusunose
    • 1
  • Yusuke Inoue
    • 1
  • Ayako Kamisato
    • 1
  • Kaori Muto
    • 1
  1. 1.Department of Public Policy, Human Genome Centre, The Institute of Medical SciencesThe University of TokyoTokyoJapan

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