Disputing the boundary of pluripotency. The Italian public debate on amniotic fluid-derived stem cells

Abstract

Amniotic fluid-derived stem (AFS) cells were the first non-embryonic source of pluripotent stem cells discussed in Italy. AFS cells have been defined “ethical stem cells”, a socio-technical label denoting an array of cellular reprogramming techniques, biological artifacts, and somatic stem cells which make it possible to obtain pluripotent stem cells while avoiding the use of human embryos. The alleged pluripotent status of these cells triggered a debate in which pluripotency was re-positioned as the most promising feature of stem cells. This debate was characterized by discursive articulations in which the boundary between multipotency and pluripotency was blurred and a discourse on a duopoly of pluripotency (pertaining both to embryonic and non-embryonic stem cells) ensued. Drawing on qualitative discourse analysis of articles in scientific journals and newspapers, this paper explores the cultural meaning and political uses of these discursive articulations in the Italian stem cell research regulation debate. This paper also examines a set of aporias emerging from the attempt to incorporate ethical stances into the biological ontology of ethical stem cells, and the problem of constructing normativities in the biotechnology field.

Keywords:

• amniotic fluid-derived stem cells
• ethical stem cells
• Italian stem cell debate and regulation

Introduction

Stem cell research is considered one of the most promising and revolutionary branches of contemporary biomedicine. The prospects of therapies and health enhancement are so closely linked to stem cells that they are embodied in several stories and narratives of hope and promise (Geesink, Prainsack, and Franklin 2008). However, this research is also a much contested socio-political issue because one of the main sources of stem cells is the human embryo, which is destroyed during the harvesting procedure. Human embryonic stem cells (hESCs) are highly valued especially because they are pluripotent (i.e. able to develop into almost any cell type). As Hauskeller and Weber (2011) pointed out, pluripotency occupies the prominent role among the biological features of hESCs, because it promises to lead to “an infinite supply of cells for the repair of damaged body tissue” (416). Put in other terms, pluripotency has been the synecdoche of the social expectations linked to stem cell research: that is, the prospects of resolving the shortage of organs for transplants, the health enhancement of an aging population, and the treatments of degenerative diseases.

As Rubin (2008) has convincingly summarized, this “therapeutic promise” clashes with the ethical dilemma of the “embryo question” – that is, the legal tutelage of the human embryo considered, especially by religious actors, as a fully human being which grants the right to life. The different regulatory frameworks on stem cell research may be seen as a balancing between these two contrasting principles, a moral trade between the (moral) value of the human embryo and the therapeutic, commercial, and social utility of hESCs (Salter 2007; Salter and Salter 2007). Indeed, as Prainsack, Geesink, and Franklin (2008) have pointed out, “it was the overarching role of the embryo in framing and structuring discourses in many countries that has rendered ‘stem cell science’ such a contested domain” (355), to the point that “the contested moral status of the human embryo diverts attention from other developments, meanings and values” (357). In other words, the embryo question has monopolized the public debate, overshadowing other ethical and social concerns and becoming the ethical issue in stem cell research.

In this paper, I shall explore a particular way to deal with ethical issues in stem cell research; one in which, instead of delegating moral evaluation to bioethics bodies or to the direct commitment of scientists in their practices, the moral problematization is incorporated in the biological objects themselves, whose ontology – or better the definitional work on their ontology – is constructed precisely in order to solve ethical quandaries through an epistemic discourse. I refer to so-called ethical stem cells, which is the label introduced into both the scientific literature and mass media discourses to denote an array of cellular reprogramming techniques, biological artifacts, and somatic stem cells which would make it possible to obtain pluripotent stem cells while avoiding the use of human embryos. In particular, I shall focus on the Italian debate on amniotic fluid-derived stem (AFS) cells (De Coppi et al. 2007) – a kind of non-embryonic stem cell defined as pluripotent – in order to explore their significance not only in the Italian context but also for a more general reflection on the construction of normativities in the regulation of biotechnological innovations.

In this paper, I critically develop some insights of Franklin (2001) and Testa (2008), who talk about the reinstallation of ethics in novel biotechnologically made life-forms. Using Gieryn's (1983, 1999) notion of boundary-work as rethought by Wainwright et al. (2006) – through the concept of ethical boundary-work – I shall explore what this reinstallation culturally means and some aporias emerging in the public discussion and political uses of ethical stem cells, with particular regard to the case of AFS cells in the Italian context. By comparing the Italian debate on AFS cells with others on different ethical stem cell sources, it is also possible to reflect on the problem of constructing normativities in the regulation of biotechnological innovations in a context where “the natural” can no longer be seen as a source of authority because it is called into question and open to manipulation (Nowotny and Testa 2010).

The cultural meaning of ethical stem cells

Wainwright et al. (2006) have pointed out that stem cell research epitomizes “the broader processes of the evolving bioscientific engagement with ethics” and the resulting obligation of scientists to commit to “ethics” (734). Moral dilemmas raised by stem cell research have been addressed mainly in two ways. On the one hand, the development of bioethics committees was one of the political means most widely adopted to deal with the tension between the embryo question and the therapeutic promise in hESC research (Gottweis, Salter, and Waldby 2009). Bioethics has emerged as the main way to fulfill “the political need to reconcile the promise of new health technologies with the cultural costs of scientific advance” (Salter and Salter 2007, 555) and as “a new language of deliberation, geared to the analysis of human values” (Jasanoff 2005, 172). In particular, public bioethics – which is “ultimately concerned with setting policies (governmental or otherwise) … [and] happens in the public sphere” (Evans 2006, 215) – appears as “a complex of institutions, practices and discourses, whose purpose is to connect policy making with ethical considerations” (Moore 2010, 198). In its interplay between institutional mechanisms and expert discourse, public bioethics is not only involved in setting policies but is also engaged with more ambitious tasks such as “ethical horizon-scanning” – i.e. “the identification and elucidation of possible ethical issues associated with new technologies” (Hedgecoe 2010, 165) – and providing a solution to the “more general problematization of scientific governance in terms of public trust” (Moore 2010, 202). Nevertheless, as the Italian case explored in the next sections shows, bioethics is not always able to resolve conflicts and tensions among different normative views and values by formulating a unifying and consensual normative framework harmonizing the competing standpoints, so that the resulting regulations are contested rather than being consensual.

On the other hand, another way to cope with ethical issues related to bioscientific innovations is what Wainwright et al. (2006) call “ethical boundary-work”, a process of social demarcation between more or less ethical ways to conduct scientific research which involves a set of perspectives, processes, and practices referring to a “practical ethics” which “takes the form of a number of choices over how to conduct oneself in a complicated political, moral and epistemic context” (Wainwright et al. 2006, 745). Nevertheless, this ethical work takes place in a space shaped by regulatory bodies; indeed, by “devolving ethics to authorities outside science” (Wainwright et al. 2006, 745), and “allowing regulating authorities to ensure [scientists’] accountability” (743), the ethical conduct of scientists “is largely underpinned by reference to the formal legal and ethical framework that defines and allows ‘ethical science’” (744). Therefore, rather than an alternative, this form of dealing with ethical issues is strictly connected to, if not even dependent on, that of public bioethics.

In this paper, I shall explore an alternative way to deal with ethical issues in stem cell research: the biotechnological construction (or the discovery) of an array of cellular reprogramming techniques, biological artifacts, and somatic stem cells which would make it possible to obtain pluripotent stem cells while avoiding the use of human embryos, namely “ethical stem cells.” The label “ethical stem cells” was proposed in 2006 (Abbott 2006; Marchant 2006) with reference to pluripotent stem cells obtained from some embryo-like biological entities. In particular, this definition was deployed for the altered nuclear transfer (ANT) technique – a procedure of somatic cell nuclear transfer which silenced the Cdx2 gene to produce an embryo unable to implant itself in the uterus (Meissner and Jaenish 2006) – and for an experiment in parthenogenesis (Paffoni et al. 2007). The protocols employed in the creation of “embryo-like structures” (Marchant 2006, 1038) were defined as intended “to satisfy the religious, ethical and/or political objections” of groups opposing hESC research (Weissman 2006, 145). The label “ethical stem cells” was also extended, in mass media discourse, to the discovery of pluripotent stem cells within non-embryonic tissues, and to the induction of pluripotency technique (Takahashi and Yamanaka 2006). Here, I focus on the alleged pluripotent stem cells discovered in the murine amniotic fluid – named AFS cells – by the team led by Anthony Atala and Paolo De Coppi (De Coppi et al. 2007).

What are ethical stem cells? They may be regarded as the outcome of what Webster terms “bio-objectification”: that is, the technoscientific creation of life-forms and “technologically enacted vital materiality” (Webster 2012, 2) which disrupts and destabilizes the “conventional boundaries and identities of biological forms” (1). Indeed, the above-mentioned embryo-like structures are novel biological entities fabricated through biotechnological procedures. But also AFS cells may be defined as bio-objects. Indeed, according to Webster (2012), aborted fetal tissue is an example of bio-objectification in which waste matter “can be re-vitalised as source material for stem cell lines” (2). Amniotic fluid, usually regarded as a waste product in childbirth or as a specimen for prenatal genetic diagnosis, was re-invented by Atala and De Coppi's team as a source of vital materiality.

Ethical stem cells represent what Franklin (2001) calls a re-engineered “ethically sensitive biotechnology” (342) obtained by “rebuilding embryonic cell lines without embryos” for the purpose of “shortcutting public opposition to research” (346). Similarly, Testa (2008) has defined ethical stem cells as attempts “to solve ethical quandaries through technological means,” since they “must be constructed, genetically and conceptually in such a way that [they are] visibly, self-evidently … biological artefacts” (441). According to Testa (2008), the deployment of these artifacts, which would make it possible to avoid the use of human embryos, is an “attractive route to depoliticize the conflict over nascent human forms” (442); and, thanks to the belief in the power of objective facts and the allegedly neutral and apolitical nature of biotechnological procedures, “molecular biology is recruited to reinforce pre-existing moral commitments” (444).

Ethical stem cells as bio-objects thus represent a paradigmatic case of Franklin's (2001) claim that in our biotechnological era “the social is literally being reinstalled within the biological” (342). According to Franklin (2005), indeed, in stem cell research, aging, health, and illness have been rethought in cellular terms; and ethical stem cells demonstrate that also ethics “can be ‘built in’ to new life-forms” (Franklin 2001, 342). By making pluripotent stem cells available while avoiding the use of human embryos, ethical stem cells would not only defuse ethical quandaries but also shift the debate from the ethical and political terrain to an epistemic confrontation grounded on the scientific reliability of these bio-objects and of the procedures producing them. This shift to a merely epistemic discourse is not only replete with cultural implications, but it is also anything but unproblematic. Gieryn's (1983, 1999) notion of boundary-work and its elaboration by Wainwright et al. (2006) offer a suitable analytical framework within which to explore aporias and contradictions generated by this reinstallation of the social in the biological.

Gieryn (1983) defines boundary-work as “part of ideological efforts by scientists” based on the

[a]ttribution of selected characteristics to the institution of science (i.e., to its practitioners, methods, stock of knowledge, values and work organization) for purposes of constructing a social boundary that distinguishes some intellectual activities as “non-science.” (782)

The starting point is the claim that in our contemporary societies science has a sort of monopoly over the “epistemic authority,” that is, the legitimate power to define, describe, and explain bounded domains of reality; therefore science “stands metonymically for credibility, for legitimate authority … for a trustable reality” (Gieryn 1999, 1). The case of ethical stem cells entails a form of boundary-work named “expansion,” which refers to the attempt by scientists to extend the epistemic authority of science, and thus its frontiers, to an ontological domain usually controlled by ethics, politics, or religion. In seeking to solve ethical quandaries by embedding them in bio-objects created to sidestep the cornerstone of ethical and political opposition to hESC research (i.e. the human embryo), the science discourse colonizes a social domain usually outside its boundaries, something seen as a jurisdiction of “the society.” Wainwright et al. (2006) have extended Gieryn's concept of boundary-work to refer to how stem cell scientists deal with bioethical issues in hESC research. They have talked about ethical boundary-work, this being demarcation between an “ethical science” and a “less ethical” conduct of research. With their differential definitions of embryo sources, scientists delineate an ethical space and a number of practical choices “to conduct oneself in a complicated political, moral and epistemic context” (Wainwright et al. 2006, 745). Nevertheless, by “drawing boundaries between what is ethically preferable” (Wainwright et al. 2006, 739) on the basis of what is prescribed by regulations, ethical boundary-work “enhances the authority of ‘non-science’ (e.g. regulatory bodies) and de-privileges science” (735). In the case of ethical stem cells, instead, the embedding of ethical issues in biotechnological procedures, protocols, and bio-objects re-evaluates “science.”

However, the use of a pure epistemic discourse on biotechnological procedure and bio-objects to cope with ethical issues (i.e. expansion) is not unproblematic, but entails aporias, contradictions and, above all, controversies on the scientific reliability and therapeutic effectiveness of different ethical stem cell sources. This is only partially due to the fact that procedures producing ethical stem cells are still in the experimental stage; as the Italian debate on AFS cells will show, other issues are at stake. First, the outcome of boundary-work is variable, changeable, and volatile, because “nature does not allow but one order of understandings” (Gieryn 1999, 17) and “there are too many ‘real sciences’” involved in boundary-work (19). Thus, along with expansion, also the boundary-work in the form of “expulsion” takes place. With this term, Gyerin (1999) refers to the discursive attempt to put the alternative understandings of nature outside the boundaries of science and deny them any epistemic authority (16). Second, a bio-object has “considerable fluidity and mobility across different socio-technical domains” and “multiple or even contrasting cultural meanings as it circulates between different sectors or networks of society” (Webster 2012, 3). Third, the blurring of the conventional boundaries and identities of biological forms enacted by the process of bio-objectification deprives nature of its moral authority. According to Nowotny and Testa (2010), “what is natural is from then on subject to the contingency” of biotechnological intervention, to the point that it “is becoming a substantially political issue” (6).

Therefore, the embedding of ethical issues in the ontology of these novel bio-objects can solve quandaries and social controversies only if they are stabilized in the epistemic domain, but this is anything but unproblematic due to their unstable and contested nature. This does not undermine the epistemic authority of science – which instead maintains the monopoly over truth discourse – but shifts the ethical debate to a boundary-work between competing understandings of stem cell biology and valuations of the clinical effectiveness and scientific reliability of different stem cell types. The case of the Italian debate on AFS cells well illustrates how this boundary-work implies aporias in establishing normativities based on understandings of nature which are instead open to controversy, and how social and political issues do not disappear but remain at stake in what seems merely epistemic disputes.

Method

This paper is based on discourse analysis carried out on articles published by scientific journals and newspapers. It explores how the pluripotent vs. multipotent status of AFS cells has been framed in scientific discourse as well as in public discussion. Mass media, and in particular newspapers, are considered as public arenas (Hilgartner and Bosk 1988), spaces of discussion and visibility in which relevant actors intervene to broadcast their standpoints and obtain public consensus for their positions. Indeed, mass media are defined as crucial sites in which public issues are framed, and in which policy struggles are played out and brought to the attention of policy-makers (Kitzinger and Williams 2005; Nisbet and Lewenstein 2002).

I collected articles published by the three most widely circulating Italian newspapers (Corriere della Sera, La Repubblica, La Stampa), the two main fora of hESC opponents (Il Foglio and Avvenire, the newspaper of the Italian Bishops' Conference), and the two newspapers linked with the major Italian political parties: Il Giornale (owned by Silvio Berlusconi, leader of the main center-right party) and L'Unità (the newspaper of Partito Democratico, the main center-left party).

On this corpus of 38 articles published from 8 January to 31 January 2007, I conducted qualitative discourse analysis which considered how the relevant actors framed AFS cells, pluripotency and multipotency, and how they used these frames in political disputes. Relevant actors comprised mainly stem cell scientists and other biologists, politicians and lay and Catholic activists. These actors were identified as relevant through previous analysis on the Italian stem cell debate (Beltrame 2012; Testa 2012) and, similarly, were grouped into two different fronts: hESC research proponents and adult stem cells (ASCs) supporters (or hESC opponents). Both fronts comprised scientists (stem cell practitioners, geneticists, and molecular biologists) as well as politicians, intellectuals, and religious and social movements’ advocates. Even if what follows is not an analysis of mass media discourse on AFS cells – since they are considered mainly as public arenas – some newspapers are treated as relevant actors in the debate; indeed, due to their editorial lines, Il Foglio and Avvenire (on the pro-ASC front), and Repubblica and L'Unità (on the pro-hESC front) acted as agents directly involved in the debate rather than as simple arenas of discussion.

The Italian stem cell regulation and ethical stem cells

Italy has endorsed a restrictive legal framework on stem cell research. As Metzler (2007, 414–415) has shown, the reordering of Italian biopolitics through the integration of Italian human embryos into the community of “citizen subjects” – enacted by Law 40/2004 on medically assisted fertilization – has prohibited Italian stem cell scientists from using supernumerary human embryos left over from in vitro fertilization treatments. With regard to stem cell research, Law 40/2004 is a paradigmatic example of how “by focusing on the centre stage of ethical and legal issues around the moral status of the human embryo, the debate keeps other developments backstage” (Prainsack, Geesink, and Franklin 2008, 357). Indeed, the embryo question was the cornerstone of Law 40/2004 and of the debate surrounding it. As has been remarked (Gottweis, Salter, and Waldby 2009; Metzler 2007), Law 40/2004 implemented the Catholic principle of “the inviolability of the innocent human being's right to life from the moment of conception until death” (Congregation for the Doctrine of the Faith 1987, emphasis added) with its first article, which declares that the basic aim is “to ensure the rights of every subject involved, including the conceived (il concepito)” (Law 40/2004, Art. 1, Sec. 1).

This reordering of the Italian (bio)polity according to Catholic doctrine was the outcome of a political struggle in which, through becoming the ethical issue in stem cell research, the embryo question also transformed “the ethical” into “the political.” Indeed, by claiming and defending the right to life of human embryos as fully human beings, Catholic actors used the Italian stem cell research debate and regulation as a means to affirm their view of the Italian social order as underpinned by the Catholic normative culture. For some conservative political parties this debate was an occasion to define their cultural and political identity as defenders of the Catholic roots of the Italian political order. By contrast, struggling for the possibility to carry out research on hESC became a means for left-wing political parties and intellectuals to assert the secular nature of the Italian political order (Beltrame 2012). The debate on stem cell research thus entered into the lay/Catholic cleavage, which is one of the most performative political divisions in Italian political life (Rusconi 2000).

The current Italian regulations emerged not from a shared consensus, but from merely political decisions based on scientific knowledge not regarded as authoritative. Indeed, the delegation to bioethics bodies – such as the National Bioethics Committee (CNB) or the ad hoc commission set up by the former Health Minister Umberto Veronesi and chaired by the Nobel-prize winner Renato Dulbecco – failed to resolve conflicts around stem cell research (Beltrame 2012; Testa 2012). Both committees were accused of ideological partisanship, and both of them split on the embryo question because the Catholic members of both committees opposed the use of human embryos for stem cell research (CNB 2000; Dulbecco Report 2000).

Numerous Italian scientists saw the current Italian regulation as an attack on the autonomy of science. They thus deployed a rhetorical repertoire based on the opposition between science and society, in which the latter was seen as being colonized by the Catholic Church's stances with their politicization of ethics (or better, with a particular kind of ethics: that of human dignity). Indeed, the proponents of hESC research argued that this field of research was ethical because, since hESCs are pluripotent, it promised to develop cures for currently untreatable diseases. This ethics of healing (Oduncu 2003) was not challenged in itself, but hESC opponents replied that biomedical innovation could be better fulfilled by research on somatic stem cells (the so-called adult stem cells, ASCs), which at the same time respected the principle of human dignity granted to the embryo. This generated an overlap between the lay/Catholic cleavage and the hESC/ASC one which was a central feature in the Italian debate (Beltrame 2012; Testa 2012) and had several consequences.

First, promoting research on ASCs acted as a powerful device, at least in terms of public communication, to contend the monopoly of hESC research over the ethical discourse on developing cures. This move shifted the debate from the opposition between the ethics of human dignity and that of healing, to a discourse centered on what kind of stem cell research trajectory could better fulfill therapeutic needs. Second, as a consequence, this struggle for monopoly over the most credible therapeutic promise moved part of the ethical debate to epistemic terrain, leaving the embryo question as the only ethical issue at stake. In other words, the discussion on the ethics of healing was transformed into an epistemic confrontation within the discourse on the biology of stem cells and on their different clinical efficacies. Instead of an opposition between science and ethics or religion, there ensued a struggle for “epistemic authority” (Gieryn 1999), a boundary-work between competing claims on clinical effectiveness and scientific reliability of different stem cell sources. Third, there developed an epistemic discourse in which ASCs were regarded as more therapeutically and clinically useful than hESCs (Testa 2012) and the pluripotency of hESCs was downgraded as useless, dangerous (i.e. tumorogenic) and as a negation of the concept of stemness, which was defined as the reparatory capacity of ASCs (Beltrame 2012).

This discourse was deployed to justify the Italian regulation on stem cell research. Indeed, in addition to the ban on using human embryos for research purposes, the possibility of carrying out research on imported hESC lines, while officially not prohibited, was seriously hampered by being denied national funding. When in 2001 the former Health Minister Girolamo Sirchia, a hematologist working on ASC, set up the first commission tasked with financing research projects on ASCs alone, he declared that stem cells obtained from adult tissues yielded results better than those of hESCs (Beltrame 2012, 215).

This regulatory framework was not only the outcome of merely political decisions, because the hESC/ASC opposition entailed a division within the Italian scientific community. Even if the majority of the Italian scientists were (and continue to be) critical of this regulation, some researchers and stem cell scientists supported this research trajectory based on ASC (e.g. stem cell scientists Angelo Vescovi and Girolamo Sirchia, the former working on fetal stem cells, the latter on hemopoietic ones). And also the most famous Italian scientific academy, Accademia dei Lincei, instead of acting as a pro-science lobby like the Royal Society in the UK (Mulkay 1994), produced a document based on a compromise between its internal parties which was not seen as an endorsement of hESC research.

This means that the Italian stem cell regulatory framework was, and continues to be, strongly contested, not only from a merely ethical and political point of view – i.e. it is seen as the outcome of religious interference in the pluralist and secular nature of the state – but also from a scientific one: according to several stem cell scientists, ASCs are not pluripotent, and therefore the Italian regulation impedes essential research on the cellular mechanism of stemness which resides in pluripotency. Law 40/2004 was challenged with an abrogative referendum in 2005 (Gottweis, Salter, and Waldby 2009; Metzler 2007) and with several appeals to the Constitutional Court; similarly, the funding policies were subject to parliamentary inquiries and an appeal to Rome's administrative court (Abbott 2009; Testa 2012).

In parallel to these direct challenges to permit hESC research, Italian stem cell scientists also sought to sidestep the regulatory framework by resorting to so-called ethical stem cells. Whilst supporters of hESC research saw in some of these cells and techniques a way to obtain pluripotent stem cells while avoiding the Italian ban on embryo research, supporters of ASCs highlighted that with these discoveries pluripotency was no longer the monopoly of hESCs and, therefore, embryo research should be considered obsolete and superseded, while the Italian decision to invest in ASCs appeared scientifically justified. In this context, the emergence of ethical stem cells, rather than solving conflicts, appeared embroiled in huge contradictions in the Italian context. Some kinds of ethical stem cells – i.e. those obtained from the creation of embryo-like structures by means of the ANT technique or through parthenogenesis – were promoted by hESC supporters to bypass the Italian ban on the use of human embryos. But these proposals resulted in much controversy in Italy because ASC supporters criticized these techniques by supporting the use of non-embryonic pluripotent stem cell sources (Beltrame 2013). Correspondingly, also the discovery of non-embryonic sources of pluripotent stem cells provoked controversies. On the one hand, these ethical stem cells would have reinforced the Italian regulations by showing the existence of an alternative to hESCs' monopoly over pluripotency. On the other hand, however, they also showed the centrality of pluripotency, contrary to the rationale underpinning the Italian regulations. It appeared contradictory that the same scientists and political actors who criticized pluripotency as clinically useless and dangerous then supported a research trajectory based on pluripotent stem cells. The wide array of cellular reprogramming techniques, biological artifacts, and somatic stem cells usually grouped under the label “ethical stem cells” was thus divided and politicized according to the hESC/ASC opposition (and therefore to the lay/Catholic cleavage), instead of defusing conflicts and solving quandaries.

In what follows I shall focus on the AFS cells (De Coppi et al. 2007), the first source of non-embryonic pluripotent stem cells discussed in the Italian public sphere. The controversy over their pluripotent versus multipotent status triggered a debate in which: (1) pluripotency was reframed and stabilized before the discussion on human-induced pluripotent stem (iPS) cells (Takahashi et al. 2007; Yu et al. 2007; see Hauskeller and Weber 2011); (2) the porous boundary between multipotency and pluripotency – and the political use of this porosity – was re-established; and (3) aporias of incorporating ethical commitments into natural ontologies were revealed, opening a debate on the relationship among science, ethics, and society. This debate, therefore, illustrates not only the contradiction on which the Italian stem cell regulation rests, but also how the emergence of ethical stem cells did not solve quandaries and conflicts in the regulation on this field of research.

(Re)stabilizing pluripotency and its boundaries

On 7 January 2007 Nature Biotechnology published on-line an article in which the team led by Anthony Atala and Paolo De Coppi declared the discovery of pluripotent stem cells discovered in the murine amniotic fluid, named AFS cells (De Coppi et al. 2007). Apparently, AFS cells, as a non-embryonic source of pluripotent stem cells, should have solved the Italian controversy on stem cell research. However, due to the scientific rationale underpinning the Italian regulations – pluripotency as dangerous and therapeutic useless – AFS cells with their alleged pluripotency raised doubts and contradictions.

Indeed, in order to mediate between the need to epistemically reinforce the Italian regulations and to avoid contradictions, pro-ASC research actors discursively managed the definition of these ethical stem cells. AFS cells were engaged in interesting boundary-work between multipotency and pluripotency and, moreover, a tactical positioning of AFS cells within this demarcation. AFS cells were defined as representing “an intermediate stage between pluripotent ES cells and lineage-restricted adult stem cells” (De Coppi et al. 2007, 103). But this cautious definition was radically modified in another passage where the authors declared that “AFS cells are indeed broad-spectrum multipotent (that is, pluripotent) stem cells” (De Coppi et al. 2007, 101, emphasis added). The article thus played on a porous and flexible boundary between pluripotency and multipotency. Indeed, the latter was not well defined, as it is the capacity to produce many (but limited) types of cell. But, discursively, this rank of cell types could be extended, and the limits reduced, by blurring the boundary between multipotency and pluripotency. In this case, “broad-spectrum multipotency” became sic et simpliciter pluripotency. Indeed, Paolo De Coppi, declared to Italian newspapers that these cells are “pluripotent like embryonic ones, that is, capable of generating any kind of tissue whatever,” since “we have employed them to generate cells of muscles, bones, nerves, liver, veins and arteries” (La Stampa, January 8, 2007).

These two definitions – i.e. AFS cells as at an intermediate stage between hESCs and ASCs, and as pluripotent – were differently deployed in the debate. Supporters of ASCs, indeed, highlighted the alleged pluripotent nature of AFS cells. For example, in Il Foglio and Avvenire, AFC cells were systematically defined as pluripotent:

The discovery of pluripotent stem cells in the amniotic fluid able to function like those extracted from embryos, … (Il Foglio, January 9, 2007, emphasis added)

Appreciation for the endeavor to find alternative ways to use embryos in order to obtain pluripotent stem cells … (Avvenire, January 9, 2007, emphasis added)

Geneticist Bruno Dallapiccola (one of the main spokespersons for the Italian pro-ASC front) described the discovery of AFS cells as demonstrating the possibility “to obtain cells with the characteristics of embryonic stem cells without destroying the embryo” (Il Giornale, January 9, 2007). Nevertheless, the contradiction with the previous discourse on pluripotency as dangerous had to be managed and defused. Indeed, even if defined as pluripotent, AFS cells were characterized as “able to reproduce several tissues without the proliferative unpredictability which renders embryonic stem cells tumorigenic” (Avvenire, January 9, 2007). In this way, the supporters of ASC research were able to recover the discourse on pluripotency and its therapeutic promise by articulating a sort of duopoly in which non-embryonic stem cells were regarded as possessing a pluripotency defined as safe and clinically useful. The overall effect was that pluripotency was re-established as the most promising feature of stem cells.

This was neither an unproblematic process nor an unchallenged discourse. Whilst ASC supporters stressed the pluripotency of AFS cells – using the equation between broad-spectrum multipotency and pluripotency – those who defended hESC research preferred the other definition, characterizing AFS cells as “a new kind of stem cells in an intermediate state between embryonic and adult ones” (L'Unità, January 8, 2007). In particular, stem cell scientists were cautious in defining AFS cells. Even a pro-ASC such as Angelo Vescovi, for example, adopted the “intermediate state” characterization, and declared that “it is yet to be determined whether they are pluripotent” (La Repubblica, January 8, 2007). And one of the discoverers of AFS cells, Paolo De Coppi, although sure of the pluripotent status of these stem cells, stated that they “are not alternative to embryonic stem cells, which are instead very useful in studying pathology models” (L'Unità, January 9, 2007).

AFS cells, thus, were not only involved in an attempt to blur the boundary between pluripotency and multipotency, but they created a sort of discourse on the duopoly of pluripotency which pertained to both ASCs and hESCs. But also this discourse was challenged. Biologist Edoardo Boncinelli (a strong supporter of hESC research in Italy) defined AFS cells as “cells which have escaped assembly of the embryo and which have multiplied themselves because the amniotic fluid is an excellent culture medium” (Corriere della Sera, January 8, 2007). In this way, AFS cells were defined as pluripotent because they originated from the embryonic cells: that is, pluripotency was reframed as a feature of hESCs, and AFS cells were removed from the family of ASC (which thus became again non-pluripotent).

This discussion on the duopoly of pluripotency and on the boundary between pluripotency and multipotency was closed by resorting to expulsion boundary-work regarding the correct understanding of the nature of AFS cells. In March 2008, Italian newspapers reported the publication in Nature Biotechnology of an article in which the Italian research team led by stem cell scientist Elena Cattaneo explained that the results of Atala and De Coppi (De Coppi et al. 2007) “do not provide compelling evidence that AFS cells can specifically differentiate into neurons” (Toselli et al. 2008, 269). The demonstration that AFS cells are not capable of generating neurons meant that broad-spectrum multipotency did not coincide with pluripotency. The boundary between pluripotency and multipotency, blurred by some definitions of AFS cells, was thus re-established. Moreover, as in the case of the debate on iPS cells (Hauskeller and Weber 2011), it was thus re-affirmed that hESCs have the monopoly on pluripotency, which in turn was re-affirmed as the most relevant and promising feature of stem cells.

Ethical stem cells and the science/society boundary

The debate on the pluripotent/multipotent nature of AFS cells shows that solving ethical quandaries by embedding them in bio-objects is not unproblematic. This is not only the case of AFS cells in Italy. Testa (2008), in exploring the fortunes of ANT techniques, has reported numerous controversies in the USA regarding the status of the embryo-like structures thus created, as well as the doubts raised with regard to the clinical and scientific reliability of the derived stem cells. Current debate on iPS cells concerns their real pluripotency compared with that of hESCs (Hanna, Saha, and Jaenisch 2010; Hauskeller and Weber 2011). hESCs still seem to be the “gold standard” with which to evaluate the real pluripotency of any given stem cell. And also in Japan – the country in which the induction of pluripotency technique was discovered – some scientists have described the “unregulated iPS cell research regime” as “reckless,” given “the limited available knowledge about the molecular processes underlying the reprogramming of somatic cells involving iPS cells” (Sleeboom-Faulkner 2011, 236–237). In Italy, the National Bioethics Committee has raised concerns regarding iPS cells, since “the significant factors in the reprogramming are oncogenic” (CNB 2009, 18). In general, the re-installation of the social (seen as a set of values and sensibilities) within the biological is not an unproblematic and neutral process; instead, it generates numerous aporias.

In the case of the Italian debate on AFS cells, the first aporia arises from a constitutive feature of ethical stem cells in general. Insofar as these bio-objects embed ethical quandaries in their biological ontology, the ethical discussion tends to transform itself into an epistemic evaluation of the scientific reliability of this ontology. This sort of expansion boundary-work, in which science defuses ethical issues with its neutral, epistemically authoritative, and objective procedures is instead embroiled in the open-ended nature of expulsion boundary-work between competing understandings of biological ontologies. Moreover, as bio-objects, ethical stem cells have a fluid and mobile nature, as well as contrasting cultural meanings (Webster 2012). In other words, these bio-objects can resolve ethical problems only if they are stabilized on the epistemic and scientific plane, but since nature is open to manipulation, and to the contingencies of biotechnological intervention, it becomes difficult to ground social and political normativities, as well as ethical principles, on such a modifiable “nature.” We have seen above how AFS cells were contested with regard to their real pluripotency, so that their ethicality was subordinated to their reliability as sources of really pluripotent stem cells and embroiled in negotiation of the boundary between multipotency and pluripotency. But even if this discussion on pluripotency and its boundaries was epistemic in nature, it was political in its aims. hESC research supporters rejected the claim of AFS cell pluripotency also in order to continue their challenge against Italian stem cell research regulation; ASC supporters, on the contrary, stressed this alleged pluripotency to defend that regulation.

A second aporia refers to the morality of the AFS cells derivation technique. Some hESC research supporters contested the ethical status of AFS cells by highlighting that the amniotic fluid is obtained through amniocentesis, a prenatal genetic diagnosis criticized as risky for the fetus and as a new form of eugenics by those who supported AFS cells. It was accordingly claimed that these ethical stem cells were not so “ethical.” Hence, the idea that a technological solution would be neutral (Testa 2008, 441) was called into question, since the biotechnological procedure itself was a matter of controversy.

A third aporia emerges with the establishment of a boundary between science and ethics. Indeed, ethics is socially constructed as a domain outside the boundaries of science, even if ethical implications are central in stem cell research. Ethical stem cells are attempts to expand the boundaries of the scientific endeavor to cope directly with ethical issues. But the translation of moral matters into an epistemic discourse in order to defuse quandaries – and thus reaffirm the autonomy of a science which colonizes also “the ethical” – leaves some question unresolved. Creating bio-objects that sidestep the use of human embryos does not permit this ethical issue to be addressed directly, and the moral status of the human embryo as a fully human subject is not called into question. In other words, the attempt to bypass the embryo question takes the moral status of the early human embryo for granted, so that the embryo question remains the cornerstone of the debate. Therefore, not only do ethical stem cells not depoliticize this ethical issue, but they also fail to de-moralize it. In the Italian case, at least, the continuous reference to the human embryo and the comparison with hESCs has the side effect that the embryo question is constantly re-affirmed as the ethical issue at stake in the stem cell politics.

The last aporia regards the ways in which ethical stem cells are located at the science/society boundary. Ethical stem cells appeared to be an attempt to protect the autonomy of science, not by challenging the ethical and political control over its conducts and practices, but by incorporating and resolving quandaries through epistemic and technical procedures. In this sense, the science/society opposition should disappear, preserving the autonomy of the former. The debate on AFS cells shows how this boundary-work between science and society generates contradictions.

For example, a hESC research supporter, Senator Ignazio Marino (a famous Italian physician), commented on this discovery by declaring:

Let us finance the science, for it will be science with its progress that resolves the ethical issues that at present seem insurmountable. In order to resolve the ethical dilemmas in this field, it is necessary to commit more funding to research (La Repubblica, January 8, 2007)

But Giuliano Ferrara, director of Il Foglio, replied to Marino and to his point of view that the discovery of AFS cells:

demonstrates once again that eschewing the logic of a single science arbiter of itself, accepting engagement with the ethical limit … may indeed be an opportunity … [this news] shows that science is steered by the resources available, which is natural, but also by the demands, pressures, and sensibility of society. (Il Foglio, January 9, 2007)

Notwithstanding differences, these two discursive articulations share a common feature: both of them hypostatize science as an a-social activity opposed to society defined as a set of ethical values and sensibilities. For the former, it is science that, by creating ethical stem cells, autonomously resolves social problems. For the latter, it is society with its sensibilities, requests, and control that directs science to fulfill its needs. AFS cells, by entering into this controversy, show how ethical stem cells are unable to resolve the tension between science and society, because for social actors this constructed distinction (and the equally constructed image of both entities) is a shared and handy shortcut to orientate themselves among the social implications of scientific development. The aporia emerges from the fact that ethical stem cells should break down this science/society barrier because they incorporate societal stances into scientific procedures and objects aimed at sidestepping social quandaries. Nevertheless, this barrier is continuously reconstructed, and AFS cells are located differently along the boundary.

AFS cells and their political use

The several contradictions and aporias involved in the ethical stem cells debate show that, even if the discussion is epistemic in nature, ethical, and political issues remain at stake. As mentioned above, the controversy over the pluripotent/multipotent nature of AFS cells, even if embroiled in boundary-work between competing understandings of stem cell biology, was aimed at challenging or defending the Italian stem cell regulation and the ethical stances underpinning it. Negating the pluripotency of AFS cells was a means for hESC research supporters to continue their challenge against the Italian regulatory framework; for ASC supporters, stressing this alleged pluripotency was functional to defending that regulation. This was clear in the use of the discovery of AFS cells in the Italian political debate on stem cell research.

Indeed, in 2005 the former University and Research Minister Letizia Moratti (center-right) decided, together with the ministers of Austria, Germany, Luxembourg, Malta, Poland, and Slovakia, to sign a document which called on the European institutions to exclude research projects involving human embryos and hESCs from financing under the Seventh Framework Programme (FP7). If this decision had succeeded, Italian researchers in the field of hESCs would have been excluded from not only national but also European Community funding. But Italy's signature was removed from this “declaration of ethics” in June 2006 by the following University and Research Minister Fabio Mussi (a left-wing politician, given that in the same year the center-left coalition won the elections). His decision provoked a strong parliamentary debate aimed at imposing the withdrawal of the so-called Mussi decision and at influencing the Italian government to impose limits to hESC research under the FP7.

The parliamentary debate rotated around the fact that this decision ran counter to the logic of the previous Italian regulation (enacted in Law 40/2004, in funding policies and confirmed by the 2005 referendum) which gave primacy to ASC research. Mussi defended his decision by stating that hESC research was fundamental, and that it was wrong to impose the restrictions of the Italian regulation on the whole European Community.

In disputing the so-called Mussi decision, center-right and Catholic politicians pointed out that the discovery of non-embryonic pluripotent stem cells demonstrated that hESC research had become obsolete, and therefore that the previous Italian regulation had been scientifically correct. Indeed, the alleged pluripotent status of AFS cells was then functional to contrasting the claim that only hESCs were pluripotent. AFS cells were thus recruited and mobilized in this debate. Contrary to the so-called Mussi decision, the senator and Catholic activist Luigi Bobba declared:

In light of this new discovery, resources have definitively shifted in favor of [this] kind of research … impeding the use of embryo stem cells. Minister Mussi should draw the consequences of this shift. The government should … use its veto to prevent the EU from financing the destruction of embryo cells. (La Repubblica, January 8, 2007)

As seen above, these actors avoided the contradiction between the downgrading of pluripotency made during the discussion on Law 40/2004 and the 2005 referendum (Beltrame 2012; Testa 2012) and its current extolling, because the alleged duopoly of pluripotency served to (re)justify previous policy choices and to contest the new one. Indeed, a similar dynamic resurfaced at the end of 2007, when with the discovery of human iPS cells, the pro-life activist Eugenia Roccella called for a five-year moratorium in order to stop embryo research in Europe. The rationale was the same: scientific developments have demonstrated that pluripotency is not a prerogative of hESCs. By accrediting pluripotency to AFS cells – or including iPS cells in the legacy of ASC research – these actors could reinforce their political and ethical choices scientifically. These “ethical stem cells” thus served to provide a scientific language with which to legitimize political choices and to embed ethical stances in an apparently neutral epistemic discourse. But, as we have seen, they also encountered aporias in the embedding of ethical and political stances in biological ontologies.

Conclusion

AFS cells, as a non-embryonic source of pluripotency, were supposed to overcome ethical quandaries by reconciling scientific innovation with societal values, sensibilities, and expectations. Nevertheless, the controversy over the biological ontology of AFS cells revealed a series of contradictions that not only lie at the core of Italian stem cell regulation but also in the discourse on ethical stem cells at large: that is, the aporias of embedding ethics in biological ontologies.

The debate on the pluripotent versus multipotent nature of these cells – and the related issue of the boundary of pluripotency – illustrates how ethical stem cells could defuse conflict only if made stable epistemically. However, this stabilization is anything but an unproblematic process, since, first, it encounters the changeable and volatile nature of the boundary-work between competing understandings of nature (Gieryn 1999). Second, ethical stem cells have contrasting cultural meanings due to circulation among different sectors of society that characterize bio-objects (Webster 2012). Finally, they are part of the process by which the natural is open to biotechnological intervention to the point that it has lost its authority and has become a political issue (Nowotny and Testa 2010). Therefore, seeking to solve ethical quandaries by embedding them in bio-objects and their (biotechnologically created) ontology runs into these contradictions.

Instead of defusing ethical and political conflicts – such as those on the ANT technique (Testa 2008) and on iPS (Hauskeller and Weber 2011; Sleeboom-Faulkner 2011) – the AFS cells debate shifted to a discussion on the reliability of their ontology and their therapeutic effectiveness. Ethical quandaries did not disappear, but took the form of a scientific evaluation: moral and political issues, which continued to be at stake, depended on and followed the stabilization of these bio-objects as functional and effective sources of pluripotent stem cells.

On the one hand, this testifies to how the epistemic authority of science is not called into question but remains the “epistemic seal of approval” (Gieryn 1999, 1) for every claim. On the other hand, however, it demonstrates the multiplicity of different understandings of a “natural” constantly made and re-made by biotechnological intervention, which renders unlikely the establishment of a normativity based on a common and shared understanding of nature.

The actors involved in these debates and committed to policy-making continue to use the natural as a source of epistemic authority to underpin normativities. However, on exploring contradictions and aporias, we must recognize that even if their discourses appear mainly epistemic in nature, they are instead political and ethical in their aims. The political use of AFS cells clearly illustrates this point. Indeed, pro-ASC research actors stressed the alleged pluripotency of AFS cells in order to defend the Italian stem cell regulatory regime and to counter the claims of the pro-hESCs front. The latter instead downgraded AFS cells to the realm of multipotent stem cells in order to claim the monopoly of hESCs over pluripotency and the related therapeutic promise, the purpose being to challenge the Italian regulations.

If ethical stem cells do not defuse conflicts and generate a shared normativity, they instead teach us that normativities in our biotechnological era are the outcome of what Jasanoff (2004) calls a process of co-production: that is, the mutual process by which knowledge of the (natural and social) world and social formations come symmetrically into being, influencing and reinforcing each other. The stabilization of bio-objects in the epistemic domain is strictly connected with the ordering of society, because these objects embed ethical, cultural, and political issues. Hence, the natural order and the normativity of “the biological” through the voice of “science” continues to appear as the bedrock for the regulatory order of “the social,” while the real normativities that underpin a regulatory order of society are instead political-epistemic assemblages which simultaneously order “the social” as well as “the natural.”