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ORIGINAL PAPER
A Preliminary Study Exploring Japanese PublicAttitudes Toward the Creation and Utilizationof Human-Animal Chimeras: a New Perspectiveon Animals Containing BHuman Material^ (ACHM)
Mayumi Kusunose1 & Yusuke Inoue1 &
Ayako Kamisato1 & Kaori Muto1
Published online: 5 September 2017# National University of Singapore and Springer Nature Singapore Pte Ltd. 2017
Abstract Ongoing research on making Bhuman-animal chimeras^ or Banimals con-taining human material^ (ACHM) to solve the shortage of organs available fortransplantation has raised many ethical issues regarding the creation and utilization ofsuch constructs, including cultural views regarding the status of those creations. A pilotstudy was conducted to explore Japanese public attitudes toward human-animal chi-meras 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 partici-pants were divided into four groups. Transcripts of the interviews were analyzed andparticipants’ attitudes categorized. Five categories of participant attitudes were identi-fied: (1) resistance to the unnatural, (2) concerns about animal welfare, (3) concernsabout controlling human-animal chimeras, (4) concerns about the possible birth ofintermediate entities, and (5) resistance to creating and utilizing animals containing mymaterial or my child’s material. Our FGI results showed a broader and greater variety ofpublic concerns than those reported in previous studies. While researchers have tried toestablish new methods to avoid creating intermediate entities, our participants
Asian Bioethics Review (2017) 9:211–228DOI 10.1007/s41649-017-0020-1
* Mayumi [email protected]
Yusuke [email protected]
Ayako [email protected]
Kaori [email protected]
1 Department of Public Policy, Human Genome Centre, The Institute of Medical Sciences, TheUniversity of Tokyo, 4-6-1 Minato-ku, Tokyo 108-8639, Japan
expressed concerns about not only intermediate entities but also animals containingtheir own material or their child’s material. Based upon their responses in the inter-views, we are introducing a new ethical concern: Banimals containing my material/mychild’s material.^
Keywords Human-animal chimeras . ACHM . Japanese public attitudes . Focus groupinterviews . Qualitative research
Background
Regenerative research addressing the chronic shortage of organs available for transplantationis continually evolving. One area receiving increasing attention is the use of stem cellmanipulation, using human embryonic stem cell (hESC) and induced pluripotent stem cell(iPSC) to foster recovery of patients’ damaged or lost functions. One approach being studiedis to create three-dimensional organs derived from a patient’s iPSCs in animal bodies: thecreation of Bhuman-animal chimeras.^ The creation and utilization of such constructs haveraised various ethical and societal concerns. To help identify and address those issues, thispaper 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 Bhybrid^ is anoffspring of two plants or animals of different species. A Bchimera^ is defined as anorganism composed of two or more genetically different types of cells, tissues, ororgans. An Bintermediate entity^ refers to human-animal chimeras that have an espe-cially human-like composition or that exhibit very human-like behaviors.
Another term, Banimals containing human material^ (ACHM), has been used inseveral studies (notably Grant and Williams (2010), the Academy of Medical Sciences(2011), and Ipsos MORI (2010) to denote chimeras composed of cells, tissues, ororgans containing human genetic material in addition to cells, tissues, and organscontaining genetic material from their own species. We follow those researchers anduse ACHM to describe the chimeras in our study.
Current Status of Research on Human-Animal Chimeras
BBlastocyst complementation^ is one of the techniques to create patient-derived organsin animal bodies. Pioneered by Hiromitsu Nakauchi, the technique entails creating, viagenetic manipulation, pig blastocysts that lack the capacity to produce a certain organ.Human iPSCs are inserted into the blastocyst to create chimeric embryos. The chimericembryos are then implanted in the pig’s uterus to be born as offspring with a humanorgan instead of the pig’s organ (Rashid et al. 2014).
If the process is successful, the new organs might be suitable for transplantation intohuman patients. The technique offers the possibility of developing patient-derivedorgans having less risk of rejection, and overcoming shortfalls in organ availability(Normile 2013; Shaw et al. 2015).
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Currently, Nakauchi and his team have successfully created rat-mouse/mouse-ratchimeras that accept the other species’ iPS-derived organs (Kobayashi et al. 2010; Usuiet al. 2012). They were also successful in producing organ-deficient pigs and allogeneicchimeric pigs (pig-pig chimeras), which they created large quantities (Matsunari et al.2013). Furthermore, they successfully cured diabetic model mice by transplanting theinsulin-producing cells of rat-grown pancreases (Yamaguchi et al. 2017). Juan CarlosIzpisua Belmonte and his team successfully made human-pig chimeric embryos in2017 (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 socialissues 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; Savulescu2011), 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 orplaying God (Cobbe 2007; Nuyen and Bioethics Advisory Committee 2010; DeutscherEthikrat 2011; Savulescu 2011), and moral humanization (Hyun 2015, 2016) havegenerated much discussion. Likewise, concerns about unknown infectious disease(Hug 2009; Nuyen and Bioethics Advisory Committee 2010; Shaw et al. 2015), animalwelfare (Fiesta and Düwell 2009; Hyun 2015; Shaw et al. 2015; Bourret et al. 2016;Hyun 2016), human exceptionalism (Fox 2016), somatechnics (Mackenzie 2016), andarguments based on emotions or intuitions such as Bwisdom of repugnance^ (Kass1997) and the Byuck factor^(Kass 1997; Midgley 2000; Nuyen and Bioethics AdvisoryCommittee 2010; Mills 2014) have similarly drawn much attention.
Research studies have also increased, including studies on the public’s perception ofthis groundbreaking technology. Wilsdon and Willis (2004) examined how scientistsand policy makers tended to focus on a framework of risk assessment for theirdiscussions, without consideration of the importance of incorporating public voicesand addressing public concerns regarding the need for such technology, who controlsthe 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 recognizingBsocial factors,^ such as beliefs, values, and assumptions, in consideration of shapingand 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 thestakeholders including the public in order to gain support for controversial scientificresearch.
Why Conduct Qualitative Research on Public Attitude Toward Human-AnimalChimeras 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 attitudeon introducing human genes into other organisms. Toi te Taiao: Bioethics Council
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(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, lossof control, loss of choice, absence of need, ethical or moral concerns, interfering withthe natural order, and concern for animals. They viewed ACHM as unnatural andagainst the spiritual aspects of nature and worried that such research was not adequatelymonitored.
Another significant qualitative study on public attitudes regarding ACHM wasconducted by a team led by Ipsos MORI in the UK (Ipsos MORI 2010). Study resultsindicated that participants found the focus group discussion sessions educational. Ingeneral, many participants became supportive of ACHM research following the ses-sions, believing it was for the greater good. They wondered about what ethical or legallimits should be placed on such research. Participants also expressed interest in theeconomic effects of the research and were leery of research and treatments beingcontrolled by large corporations and/or the wealthy. However, they were confident thatgovernmental regulations would effectively address their apprehensions.
In Japan, two quantitative studies have been conducted on human-animal chimeraresearch. Inoue et al. found that about 50% of Japanese citizens were against researchthat entailed the creation of human-animal chimeras, while a majority of researchersapproved of such studies (Inoue et al. 2016). These results contrasted with a 2016quantitative study assessing public attitude toward creating human-pig chimeras usingblastocyst 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 Byes/no^ answers. Ormandy andSchuppli (2014) stressed the importance of qualitative research, arguing that B[w]henrestricted 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 policymakers to understand the nuance in attitudes in order to make progress in addressingsocietal concerns^ (Ormandy and Schuppli 2014).
A qualitative approach to researching public perceptions on ACHM had not beenconducted in Japan. Our research and analysis will help to clarify the public’s expec-tations and concerns regarding this technology and provide basic data for futurediscussions and research.
Methodology
Our pilot study consisted of focus group interviews (FGIs) conducted with citizensfrom the Greater Tokyo Area. The study design was adapted from the survey/ FGImethodology employed in Ipsos MORI’s 2010 study of public attitudes regardingACHM in the UK. MORI’s study focused on the same topic and issues as ours andoffered the opportunity to compare our results with MORI’s more comprehensivestudy.
FGIs are a well-established method for exploring the views of individuals in a groupsetting. The group setting of FGI encourages communication through the dynamicinteraction of the group members, which can be advantageous in helping participantsformulate opinions on unfamiliar topics, unlike the personal interviews (Kitzinger
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1994). FGIs have been used to explore people’s expectations and risk perceptions ofnew technologies in many studies on genetic modification topics; genetic screening orcarrier 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; Eijkholtet al. 2012).
The protocol of this research was approved by the institutional review board at theInstitute 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 preliminarysurvey measuring attitudes toward ACHM. In order to explore attitudes of widercommunity in the Greater Tokyo Area, people exhibiting a strong connection withanimals, religion, or medicine were excluded from the final list of participants. Theparticipants consisted of six males and six females in their 20s and 30s, and six malesand six females in their 40s and 50s. Participants were divided into four focus groupsconsisting of a single sex and age range (Table 1). Each focus group was interviewed in2-h sessions held in Tokyo on February 25 and 26, 2012.
Before the interviews, we prepared an interview guide and 40 flip boards containingpictures and illustrations of fundamental information corresponding to the discussiontopics. A professional facilitator was made available to respond to questions about thescientific aspects of the topic.
In our FGIs, the participants were asked to answer and discuss sequentially thefollowing questions:
(1) Degree of familiarity with chimeras and chimera studies(2) Attitude about the use of animals as research subjects(3) Attitude about implanting animal materials into humans (and more specifically,
the research participants and their families)(4) Attitude about producing and utilizing individual animals for the purpose of
resolving organ shortages(5) Animal species that would be acceptable to be produced and utilized for
medical purposes(6) Organs that would be acceptable for regeneration within animal bodies and
utilization for medical purposes(7) Degree of familiarity with current regulations regarding chimera studies in
regenerative medicine
Unlike MORI’s study, in which UK participants received information on ACHMprior to the FGIs, Japanese participants received less information on chimeras beforethe interviews because one of our goals was to observe the initial reactions and honestfeedback 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 wassifted, thematically sorted, and analyzed. We carefully considered the actual words usedand their meanings, context, frequency, intensity, specification of responses, internalconsistency, big ideas, and the participants’ perceptions of importance. Following thisinitial analysis, the segments identified as meaningful information were extracted and
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Tab
le1
Participants’characteristics
Group
AA-1
A-2
A-3
A-4
A-5
A-6
Sex
Female
Female
Female
Female
Female
Female
Age
2928
2837
3037
Maritalstatus
Single
Single
Single
Married
Married
Married
Occupation/industry
Law
Manufacture
Realestate
Housewife
Housewife
Educatio
n
Group
BB-1
B-2
B-3
B-4
B-5
B-6
Sex
Male
Male
Male
Male
Male
Male
Age
4148
4257
4753
Maritalstatus
Single
Married
Married
Single
Single
Married
Occupation/industry
Automanufacture
Electronicmanufacture
Hospitalindustry
Finance/insurance
Realestate
Automanufacture
Group
CC-1
C-2
C-3
C-4
C-5
C-6
Sex
Female
Female
Female
Female
Female
Female
Age
4045
4751
5254
Maritalstatus
Married
Married
Married
Married
Married
Single
Occupation/industry
Housewife
Housewife
Hospitalityindustry
(tem
porary)
Realestate(self-em
ployed)
Housewife
Distributionsales(part-tim
e)
Group
DD-1
D-2
D-3
D-4
D-5
D-6
Sex
Male
Male
Male
Male
Male
Male
Age
2827
2038
3939
Maritalstatus
Single
Single
Single
Married
Married
Single
Occupation/industry
Realestate
Student
Student
Publicoffice/foundation/
incorporated
association
Manufacture
Softwaredevelopm
ent/S
I/multim
edia
contentsdevelopm
ent
Total:24
216 Asian Bioethics Review (2017) 9:211–228
categorized. Once all the group interview data had been processed, the categories werecompared and organized. At the stage of final analysis, a chart was created to compareall the items and categories, which were then rearranged into appropriate thematicgroups.
In the following sections of this paper, we will mainly discuss the findingsregarding Battitudes about producing and utilizing individual animals for thepurpose of resolving organ shortages.^ This was the primary rationale forconducting the pilot study and is one of the internationally discussed issuesthat may trigger regulatory changes in this field and possibly profoundly affectthe relationship between humans and animals in both the biomedical andsocietal contexts. Our findings, though preliminary, offer new informationregarding perceptions regarding human-animal chimeras.
Results
Most participants did not have any knowledge about studies on the creation of humanorgans inside animal bodies. However, in conjunction with utilizing informationprovided by the facilitator, they shared relevant information that they thought theyhad acquired through newspapers, TV, comics, and science fiction animation andmovies to discuss the topics.
Our results identified four thematic groups for the topic of Battitudes about produc-ing and utilizing individual animals for the purpose of resolving organ shortages^: (1)resistance to the unnatural, (2) concerns about animal welfare, (3) concerns aboutcontrolling human-animal chimeras, (4) concerns about the possible birth of interme-diate entities, and (5) resistance to creating and utilizing animals containing mymaterial/my child’s material. Participants’ responses included in the discussion havebeen translated by the authors into English from Japanese.
Resistance to the Unnatural
Most participants in our FGIs had a tendency to value Bnature.^ They considered naturein itself to be good. Manipulation of natural objects was unacceptable to most partic-ipants. Some expressed strong resistance to the creation and utilization of human-animal chimeras, because these entities would not include natural features that distin-guish them from ordinary animals. In particular, they viewed the creation and thenkilling of unnatural entities solely for transplantation purposes as unnecessary.
Well, though it might be safer to use organs consisting of human cells… In thecase of a baboon, a natural-born baboon was killed so that its heart could betransplanted; but in this [human-]pig [chimera]’s case, humans would artificiallycreate an organ-deficient pig on purpose, and manage it so that it is born; what ismore, a pig would be implanted with human cells, and then the pig’s heart wouldbe taken out for human’s preferences; consequently, the pig would die because itlost its own heart. I feel the pig was forcibly created for my own sake.(Female in her 20s)
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One of her concerns was that manipulating the birth and death of human-animalchimeras 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 fororgans. I don’t think I would receive a transplant; instead, I think I would justaccept my natural life. I guess it is the same reason that the number of transplantsdoes not increase. I believe it is good to let nature take its course. Well, it is okayto extend life with an operation or something, but I believe it is not necessary totry it [to create chimeric animals] forcibly by destroying natural entities. (Femalein her 40s)
Other participants shared this women’s view of using nature as the criterion of theacceptability of death. For them, a natural death was better than a longer life achievedthrough the use of life-prolonging procedures, including organ transplantation, espe-cially if it involved the creation of chimeras.
Similarly, some participants expressed the opinion that manipulation ofnatural objects might cause harm to human beings. These sentiments werederived not only from the negative attitude toward the violation of the naturalorder but also from an anxiety arising from safety issues. Most participantsdisplayed a cautious attitude toward genetically modified materials becausethere was no guarantee about the long-term safety of intake of geneticallymodified substances. They believed that the consumption of natural materialsguaranteed long-term safety of the human body.
Overall, Japanese participants valued what they perceived as a natural order andconsidered 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 modifiedand manipulated although they acknowledged the necessity of animal experimentationfor medical developments.
I feel pity for animals that are genetically manipulated, though I understand theexperiments are important. (Female in her 20s)
Other participants expressed concern about the vulnerability of animals beingexploited.
… It is because ‘buta-san’ [‘the piggy’ or ‘Mr. Pig’] could not create its own heartfrom the beginning that human cells would be implanted. What is more, genemodification would be employed to produce ‘buta-san’ without a heart. I am veryconcerned about those things. I feel pity. (Female in her 20s)
In her perspective, organ deficit pigs are being deprived of their own organs andsince they cannot create their own organs, they were made to rely on human cells and
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human intervention to survive. This remark provided insights into how entities inresearch were viewed as vulnerable, as well as a less anthropocentric perspective.
Interestingly, participants called human-pig chimera as Bbuta^ at the beginning ofthe interview, but as the discussion progressed, the participants began to call it Bbuta-san.^ In Japanese, Bbuta^means Bpig^ and B-san^ is a suffix to be added after a noun toreference the subject with politeness. Regardless of age and sex, the Japanese partic-ipants tended to describe pigs with a suffix as Bbuta-san^ (BMr. Pig^ or piggy), whenthey talked about sacrificing pigs in research. This may be anthropomorphizing theirfeelings onto the pig, or it could be recognition of the pigs as living creatures rather thanBobjects.^
Concerns About Controlling Human-Animal Chimeras
Many participants expressed concerns about the impact that creating and utiliz-ing human-animal chimera would have on humans. They wondered about whatcould happen if humans became unable to control them. They worried that thehuman-animal chimera might jeopardize humans and their natural environmentif they escaped.
… Make sure to get [human-animal chimeras] controlled. Talking about controlmight sound extremely ambiguous, but let’s say such odd pigs are born anddestroy 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 usbeyond repair if mankind became unable to control the chimeric animals. I amafraid that mutant or new organisms which mankind could not control might beborn. (Male in his 30s)
Another participant criticized the idea that human-animal chimeras should beexterminated 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 inhis 40s)
Concerns About the Possible Birth of Intermediate Entities
Participants expressed concerns about the possible birth of intermediate entities, theirethical rights, and questioned the boundaries between humans and animals.
The closer [to humans the animals become], the more suitable for transplant theywould be; but when animals get closer and closer to human beings, it leads to aboundary issue whether they should be considered as humans or animals.(Female in her 50s)
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… I wonder how people or countries that supported the experiments would takeresponsibility if an intermediate entity were to be born, generated his ownconsciousness, and doubted his own existence. The chances of such a case mightbe very slim; but due to human errors, I don’t think it could never happen. I dobelieve there is some probability that a therianthrope or human-pig chimera mightbe created for real. I feel a bit scared when I imagine him asserting his humanrights even though he was similar to a pig. (Male in his 40s)
These participants raised concerns about the social status of intermediate entitieswith a human-like appearance or with self-consciousness. Others expressed concernsover whether we should provide some form of human rights to these intermediateentities, and who would take responsibility for them if they were born.
Resistance to Creating and Utilizing Animals Containing MyMaterial/My Child’sMaterial
Some participants showed strong concerns about utilizing human-animal chimerasthat contained their own genetic material, or their child’s genetic material. Mothersshowed especially strong feelings about the creation of animals that included theirown child’s material; they tended to manifest concerns about not only using thehuman-animal chimera but also creating them. They viewed such creatures ashaving a special status. The presence of their own or their child’s genetic materialmade 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 inkilling something that inherited my genes. (Male in his 20s)
As I said before, despite the shortage, I still feel resistance to create a creature thatcontains my cells and eventually kill it; in that case, I think it would rather bebetter to choose baboons for transplantation. Though I wonder what kind ofanimal 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’ owncells as family and compared their creation and use to using their own children fortransplantation purposes, or Bmy child.^
Suppose the opposite situation, I mean putting a human in the pigs’ situation; inthat situation my child is growing in mom’s belly; then I would be asked if Iwanted to kill the child and have its heart transplanted. In other words, the onlydifference 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. Eventu-ally… Well, if it were not a pig but a human, it is surely the same as killing myown child. (Male in his 30s)
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Participants also expressed concerns and opposition to creating ACHM that containtheir own child’s genetic material.
I am against it. I cannot do such things with taking the risk of what kind of entitywould be born. The pig that has my child’s cells eventually dies, doesn’t it? Eventhough I think it is on behalf of my child, I cannot insist on pursuing my ego nomatter what happens. (Female in her 40s)
Even more, the entity that has my child’s cells would be created. That is thebiggest problem. (Female in her 40s)
Perceiving the chimera with their genetic material as special or family, participantsquestioned and expressed concern about how the chimera’s body would be handledafter 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 withoutmercy, 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 stronglyembedded in Japanese culture. It appears that the participants believe that a chimericbody should be treated with respect and dignity because it contained a human adult orchild’s materials.
Discussion
Comparison Between the Japanese Participants’ Attitude and the UK’s PublicAttitude
Comparing our results to those of MORI’s UK study, we find many differences and thatmay be based on cultural attitudes toward, as well as perceptions of, human-animalchimera.
We found three main differences in public attitudes. First, the Japanese participantsin our study predominately opposed human-animal chimera research. The only excep-tions were men in their 20s. Of special note, most Japanese participants repliednegatively when they were asked whether they would accept an organ nurtured insideof a chimeric animal. This contrasts with UK FGI results where each group, regardlessof 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 distri-bution of the benefits from human-animal chimera research would be achieved (IpsosMORI 2010, p. 5). Only one participant in our study raised that issue. Other partici-pants were more concerned about the creation and nature of the chimeras.
Third, UK participants expressed greater trust in the adequate enforcement ofregulations dealing with chimera research than participants in our study (Ipsos MORI
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2010, p. 5). Our participants expressed skepticism about the effectiveness of the currentJapanese regulatory system.
Both studies reveal a number of similarities in participant perceptions. Both studyparticipants expected benefits from medical developments, but they worried about thepossibility 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 chimerascompared to humans. They also worried about regulatory compliance and enforcement,fearing that human-animal chimeras might jeopardize humans and their natural envi-ronment if not adequately controlled, which has been framed as an ecological riskargument (Fiesta and Düwell 2009).
Overall, participants in both MORI’s UK study and our pilot study in Japan voicedsimilar responses to most of the FGI discussion items. The one item which yielded aclear cultural/perceptual difference was item (4), which relates to attitudes aboutproducing and utilizing individual animals for the purpose of resolving organ shortages.In our study, participants expressed resistance to creating and utilizing animals con-taining either their own or their child’s genetic material. No similar outlook wasdetected in UK participants. This finding has important implications for ACHMresearch worldwide and for Japan in particular.
Japanese Participants’ Attitude Toward BHuman-Animal Chimeras,^or BAnimals Containing Human Material^
We identified five response groupings for our study’s findings on FGI item 4: attitudesabout producing and utilizing individual animals for the purpose of resolving organshortages. In an earlier section of this paper, we dealt in detail with each responsegrouping. Responses for the first four groupings were similar to those found in the otherresearch studies mentioned earlier in this paper. However, the fifth issue Bresistance tocreating and utilizing animals containing my material/my child’s material^ yieldedcomments that are so different from other study results that they reveal what may beconsidered a unique perspective inherent in research into producing organs insideanimal bodies by employing autologous iPSC transplantation technologies.
New Perspective: Not Just BAnimals Containing Human Material^ but BAnimalsContaining My Material^ (ACMM)
Participants in our study—regardless of age or sex—expressed particular perspectivesand feelings toward chimeras containing their own cells or their child’s cells. Duringthe FGI, we observed that how participants described human-pig chimeras changedfrom 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 ourFGIs initially gave to the human-animal chimeras changed from Bthe outsider,^ Bthehazardous entity,^ and Bthe expendable animals^ to Bthe entity that shared some partswith themselves^ or Bthe entity whose existence had a special significance for them.^Ultimately, such human-animal chimeras were no longer just laboratory animals orexpendable animals for medical use, but had morphed into an entity entitled to respect
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and a type of social status. The change in perception indicates a status change whenparticipants’ own genetic material is used. Participants began to move beyond thepersonal connection to a societal/cultural one when discussing disposal of the chimera’sbody.
In the Japanese culture, it is customary for people to keep their/their children’s bodyparts, such as umbilical cord, infant’s hair or teeth, as symbols or tokens of associationor celebration of growth (NTT DATA 2017). Japanese people retain a relationship withdeparted friends or relatives through preserving body parts of their loved ones. Similarthings can be seen in relationship between donors’ family and a recipient in organtransplant. We sometimes hear the family members of some organ donors say that theirson or daughter is still living in the recipient’s body.
The perception concerning chimeras containing Bmy material^ is dissimilar to theissues of chimeric animals with human-like external features discovered during pre-natal examination discussed by Bourret et al. (2016). In our study, the human featuresof chimera are derived from Bmy cells^ or Bmy child’s cells^ and do not entail anyhuman-like external features. It is the donated cells, not external appearance, whichcreates the attachment between donor and chimera. It is the cell donor who has causedthe pain and suffering endured by the animals containing their materials, especiallywhen the donation is predicated on a creature being deprived of its natural organs, orresults in the death of the chimera. Recognizing their role in the situation create, formany people, complex feelings of attachment, affection, and/or guilt toward the abortedhuman-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 wasdone, a decision would be required on how to deal with the redundant chimeras, thesiblings of the life-saving chimera animal. The perceptions that our study has uncov-ered suggest that each redundant chimera would be considered as having a relation toits human donor and deserving of a status higher than a mere Bobject.^ The psycho-logical impact on donors must be considered when addressing ACHM concerns.
Beyond our study, the famous Henrietta Lacks story is another example ofperceiving chimeras containing human genetic material as more than Bobjects.^In the Lacks story, Henrietta’s cells (HeLa cells) have been distributed globallyfor medical science advancement. For researchers, the HeLa cells are just cellsor 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 Henriettaor Bmother^; the family found special meaning in the cells and felt connectedwith the deceased individual (Skloot 2010). The lesson to be learned from thestory behind the HeLa cells is that behind the scientific research that useshuman materials, the perceptions of research participants, patients, and theirfamilies need to be taken into account.
While issues such as species, dignity, and moral status have been heavily discussedin the ACHM literature, little attention has been given to the perspective of Banimalscontaining my material^ or Banimals containing my child’s material,^ related to asso-ciation and attachment among cell donors, their family, and chimeric animals.
If researchers and policy makers consider public understanding as important, per-ceptions like those of our FGI participants must be considered when analyzing whypeople may oppose creating human-animal chimeras in research. Their views must be
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addressed and incorporated into the discussion, and not dismissed as justanthropomorphism.
BInterspecies Conceptus Complementation^ and FGI Participants’ Concerns
Reflecting on the concerns raised regarding the ethical and social implicationspertaining to the creation and utilization of human-animal chimeras, researchers havetried to establish new methods. For instance, some researchers proposed a new method,called Binterspecies conceptus complementation,^ as an alternative to blastocyst com-plementation. In this method, progenitor cells, instead of iPSCs, are injected into thetargeted place of an embryo at the right time to ensure that human cells do not mix withanimal 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 publicconcerns, and the arduous efforts of researchers to avoid such an outcome should beacknowledged. However, the participants in our FGIs did not distinguish betweenchimeras and intermediate entities since both types of entities would contain theirown material or their child’s material. Our results suggest that mere creation of chimericanimals with Bmy material^ or Bmy child’s material^ may invoke people’s anxiety.Furthermore, mixing animals with Bmy material^ or Bmy child’s material^ might alsobe one of the unpalatable factors, or so-called Byuck factors,^ for some people. In thiscase, there are gaps between people’s concerns, as expressed in our FGIs, andresearchers’ responses to address issues concerning the creation and utilization ofhuman-animal chimeras.
In conclusion, our FGI results showed a broader and greater variety of publicconcerns than those reported in the previous studies. From the new perspective ofBanimals containing my material/my child’s material^ that our study has unveiled, wesuggest that it is important and necessary not only to consult with various experts, butalso to incorporate a broad range of public perspectives by facilitating public dialogwith 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 agreewith research that is tainted with ethical problems just because their knowledge of theresearch increases. They believe that it is not prudent for scientists and policy makers toexpect that well-informed citizens would automatically support any and all scientificresearch (Evans and Durant 1995). It should be noted that gaining public understandingfor human-animal chimera research by providing only scientific knowledge is notenough. Thus, we expect that the perspective derived from our FGI will help to fillin the understanding gap between researchers and the public.
In sum, we recommend that regulation and preventive safeguards be further con-sidered through greater communication and explanation to address the concerns iden-tified in our study. We also recommend that researchers and policy makers explain thestatus of regulation and compliance of researchers concerning human-animal researchand how regulation has effectively prevented the situation that ordinary people areconcerned about.
In response to concerns about animal welfare, it is important for researchers topractice, at least, the Bthree Rs^ (replacement, reduction, and refinement). We alsorecommend that researchers explain the reasons for using animals in research; how
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human-animal chimeras, including redundant creations, are dealt with; and how toreduce 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 thelimitations of our research. Firstly, being an exploratory study, our research needsfurther validation. Secondly, although we collected the data necessary to enable furtherresearch—through compiling the meaningful discussions held among the participants,our sample size is too small to generalize our findings. More specifically, our samplewas limited to the Greater Tokyo Area. Moreover, our sample did not include individ-uals with strong views about medicine, religion, or animals. Therefore, we consider itimportant for future research to include the views of people who have experiencedserious health problems, participants who are strongly religious, and those who con-sider animal welfare to be important.
Acknowledgements We would like to thank the citizens who participated in the focus group interviews. Weacknowledge the contributions and helpful suggestions of Professor Hyunsoo Hong and members of theDepartment of Public Policy at the University of Tokyo as well as Dr. Shimon Tashiro at the National CancerCenter for helpful suggestions. Additionally, the authors would like to express special gratitude to ProfessorHocine Fetni at the University of Pennsylvania and Professor Robert Congleton of Rider University for editingthe English paper and their valued advice.
Funding Information This study was funded by Japan’s Ministry of Education, Culture, Sports,Science and Technology, the Japan Science and Technology Agency, and the Japan Agency forMedical Research and Development.
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 institutionalreview board (IRB) at the Institute of Medical Sciences, The University of Tokyo (approval number: 23-63-0223, date of approval: February 23, 2012).
References
Academy of Medical Sciences. 2011. Animals containing human material. United Kingdom: The Academy ofMedical Sciences. Available at www.acmedsci.ac.uk/download.php?file=/images/project/Animalsc.pdf.Accessed 11 May 2016.
Bourret, R., Martinez, E., Vialla, F., Giquel, C., Thonnat-Marin, A., and De Vos, J. 2016. Human-animalchimeras: ethical issues about farming chimeric animals bearing human organs. Stem Cell Research &Therapy 7(1): 87.
Boyatzis, R.E. 1998. Transforming qualitative information: thematic analysis and code development. TheUnited States of America: Sage Publishing.
Cobbe, N. 2007. Cross species chimeras: exploring a possible Christian perspective. Zygon 42 (3): 599–628.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.
Asian Bioethics Review (2017) 9:211–228 225
Ehrich, K., Williams, C., and Farsides, B. 2008. The embryo as moral work object: PGD/IVF staff views andexperiences. Sociology of Health & Illness 30(5): 772–787.
Ehrich, K., Williams, C., and Farsides, B. 2010. Fresh or frozen? Classifying ‘spare’ embryos for donation tohuman embryonic stem cell research. Social Science & Medicine 71(12): 2204–2211.
Eijkholt, M., Kwon, B., Mizgalewicz, A., and Illes, J. 2012. Decision-making in stem cell trials for spinal cordinjury: the role of networks and peers. Regenerative Medicine 7(4): 513–522.
Evans, G., and Durant, J. 1995. The relationship between knowledge and attitudes in the public understandingof science in Britain. Public Understanding of Science 4(1): 57–74.
Fiesta, A., and Düwell, M. 2009. IV. Ethics—ethical issues raised by chimera and hybrids—an overview. InCHIMBRIDS−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.
Fox, M. 2016. What is special about the human body? Law, Innovation and Technology 7: 206–230.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.
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 athttp://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780195371963.001.0001/oxfordhb-9780195371963-e-25. Accessed 20 April 2017.
Guest, G., MacQueen, K.M., and Namey, E.E. 2011. Applied thematic analysis. The United States of America:Sage Publishing.
Hug, K. 2009. Research on human-animal entities: ethical and regulatory aspects in Europe. Stem CellReviews 5: 181–194.
Hyun, I. 2015. From naive pluripotency to chimeras: a new ethical challenge? Development 142: 6–8.Hyun, I. 2016. What’s wrong with human/nonhuman chimera research? PLoS Biology 14: e1002535.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.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.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.
Karpowicz, P., Cohen, C.B., and Van der Kooy, D. 2004. It is ethical to transplant human stem cells intononhuman embryos. Nature Medicine 10(4): 331–335.
Karpowicz, P., Cohen, C.B., and Van der Kooy, D. 2005. Developing human-nonhuman chimeras in humanstem cell research: ethical issues and boundaries. In CHIMBRIDS−Chimeras and Hybrids inComparative European and International Research− Scientific, Ethical, Philosophical and LegalAspects, eds. J. Taupitz and M. Weschka, 535–555. Berlin: Springer.
Kass, L.R. 1997. The wisdom of repugnance: why we should ban the cloning of humans. New Republic 216:17–26.
Kitzinger, J. 1994. The methodology of focus groups—the importance of interaction between researchparticipants. Sociology of Health & Illness 16: 103–121.
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 byinterspecific blastocyst injection of pluripotent stem cells. Cell 142: 787–799 Available at http://www.sciencedirect.com/science/article/pii/S0092867410008433 Accessed 11 May 2016.
Kobayashi, T., Kato-Itoh, M., and Nakauchi, H. 2014. Targeted organ generation using Mixl1-induciblemouse pluripotent stem cells in blastocyst complementation. Stem Cells and Development 24(2): 182–189.
Mackenzie, R. 2016. Queering Spinoza’s somatecnics: stem cells, strategic sacralisations and fantasies of careand kind. In Somatechnics: queering the technologisation of bodies. Kindle ed, ed. S. Murray. New York:Taylor and Francis.
Marris, C., and Rose, N. 2010. Open engagement: exploring public participation in the biosciences. PLoSBiology 8(11): e1000549.
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 complementationgenerates exogenic pancreas in vivo in apancreatic cloned pigs. Proceedings of the National Academy ofSciences 110(12): 4557–4562 Available at http://www.pnas.org/content/early/2013/02/13/1222902110.abstract Accessed 11 May 2016.
226 Asian Bioethics Review (2017) 9:211–228
McClaren, B., Delatycki, M., Collins, V., Metcalfe, S., and Aitken, M. 2008. ‘It is not in my world’: anexploration of attitudes and influences associated with cystic fibrosis carrier screening. European Journalof Human Genetics 16(4): 435–444.
Midgley, M. 2000. Biotechnology and monstrosity: why we should pay attention to the Byuk factor .̂ HastingsCenter Report 30 (5): 7–15.
Mills, C. (2014) Commentary: In defence of repugnance. Akabayashi, A. (Ed.). The future of bioethics:international dialogues. Oxford University Press. pp. 366-370.
Mixed Media Limited. 2004. Report to the bioethics council on the dialogue events focusing on human genesin 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.
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.
Normile, D. 2013. Chimeric embryos may soon get their day in the sun. Science 340 (6140): 1509–1510Available at http://www.sciencemag.org/content/340/6140/1509.summary (accessed May 11, 2016).
NTT DATA Institute of Management Consulting, Inc. 2017. Social awareness survey on regenerativemedicine: the key to donate human cells for regenerative medicine is adjusting the environment todonors’ preferences. Japan: NTT DATA institute of management consulting, Inc. (Japanese). Availableat: http://www.keieiken.co.jp/aboutus/newsrelease/170307/ Accessed 1 Sep 2017.
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.
Ormandy, E.H., and Schuppli, C.A. 2014. Public attitudes toward animal research: a review. Animals (Basel)4: 391–408.
Palacios-González, C. 2015a. Human dignity and the creation of human–nonhuman chimeras. Medicine,Health Care and Philosophy 18: 487–499.
Palacios-González, C. 2015b. Ethical aspects of creating human-nonhuman chimeras capable of humangamete production and human pregnancy. Monash Bioethics Review 33: 181–202.
Porter, M., and Bhattacharya, S. 2005. Investigation of staff and patients’ opinions of a proposed trial ofelective single embryo transfer. Human Reproduction 20(9): 2523–2530.
Rashid, T., Kobayashi, T., and Nakauchi, H. 2014. Revisiting the flight of Icarus: making human organs fromPSCs with large animal chimeras. Cell Stem Cell 15: 406–409.
Robert, J.S., and Baylis, F. 2003. Crossing species boundaries. American Journal of Bioethics 3(3): 1–13.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.
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.
Sawai, T., Hatta, T., and Fujita, M. 2017. Public attitudes in Japan towards human–animal chimeric embryoresearch using human induced pluripotent stem cells. Regenerative Medicine. 12: 233-248.
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 qualitativestudy. Genetics in Medicine 14(1): 76–80.
Shaw, D., Dondorp, W., Geijsen, N., and de Wert, G. 2015. Creating human organs in chimaera pigs: anethical source of immunocompatible organs? Journal of Medical Ethics 41(12): 970–974.
Skloot, R. 2010. The immortal life of Henrietta Lacks. Reprint ed. New York: Crown.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.
Usui, J., Kobayashi, T., Yamaguchi, T., Knisely, A. S., Nishinakamura, R., and Nakauchi, H. 2012. Generation ofkidney 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 11May 2016.
Asian Bioethics Review (2017) 9:211–228 227
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.
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., NunezDelicado, E., Lajara, J., Guillen, I., Guillen, P., Campistol, J.M., Martinez, E.A., Ross, P.J., and IzpiuaBelmonte, J.C. 2017. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168: 473–486e15. Available at http://www.cell.com/cell/pdf/S0092-8674(16)31752-4.pdf Accessed 20 April 2017.
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 athttp://www.nature.com/nature/journal/v542/n7640/abs/nature21070.html?lang=en Accessed 20 April2017.
228 Asian Bioethics Review (2017) 9:211–228