Framing pluripotency: iPS cells and the shaping of stem cell science

Abstract

In the last decade, the pluripotency of human embryonic stem cells, i.e. their capacity to differentiate into any cell of the body and multiply endlessly, has encouraged visions and hopes for a new regenerative medicine. However, research with human embryos and cells derived from them is ethically controversial and different regulatory frameworks have developed across countries. In 2007, induced pluripotent stem (iPS) cells were generated that have been framed as a scientific breakthrough, which may provide an ethical alternative to embryonic stem cells. Drawing on interviews with embryonic stem cell researchers in Germany and the UK this article examines how scientists relate to iPS cells as new research objects. We show how three different aspects of stem cell science, namely ethical debate, therapeutic expectations and scientific uncertainty are tied together in the scientists' understanding and evaluation of different kinds of pluripotent stem cells. Furthermore, we show how the cells are set within a meaningful trajectory of scientific development that serves to justify previous and new research practices and stabilizes stem cell research as a field of scientific investigation. As a result, the article contributes to an understanding of the performative shaping of stem cell research as a contested and uncertain field of research.

Keywords:

• induced pluripotent cells (iPS)
• stem cell research
• emerging science
• ethics and regulation

Introduction

Research in human biology today is dominated by a therapeutic imperative and ethically contested research practices are commonly defended with reference to future medical cures. This development of biomedicine in the past half century has been accompanied by a shift towards understanding and manipulating vital processes at the molecular level (Rabinow 1996, Clarke et al. 2003, Rose 2007). Cells in particular have become favored sites of technical intervention (Franklin and Lock 2003, Landecker 2007) with stem cells as a recent major area of inquiry and experimentation that carries high expectations as a promising line of work for a future regenerative medicine.

One important area in this field is research with human embryonic stem cells (hES cells), i.e. cells taken from human embryos in vitro that are only a few days old. The special character of hES cells for regenerative medicine is their pluripotency, i.e. their capacity to divide endlessly and develop into all cells of the body. Managing pluripotent hES cell lines may lead to an infinite supply of cells for the repair of damaged body tissue. But the science is in its infancy and its findings and future applications are uncertain.

HES cell research has raised much ethical criticism and public debate across countries because it presupposes the destruction of human embryos. Some countries have outlawed research on hES cells, and many countries strictly regulate the use and creation of human embryos for research. Since the first derivation of hES cells in 1998, scientists have worked on identifying other sources of pluripotent stem cells. When in 2007 Japanese and US researchers generated induced pluripotent stem cells (iPS cells) from adult human cells, this was celebrated as carrying great medical potential and providing an ethical alternative to hES cells.

This article presents an analysis of how researchers working in hES cell research respond to and make sense of the emergence of iPS cells as a novel object, that may benefit or threaten existing research practices. Drawing on interviews conducted during the year after the first publication on human iPS cells, this article demonstrates how researchers working on hES cells in Germany and the UK construct a scientific pathway in light of the new pluripotent kind of cell, in which the biological, medical and ethical properties of their objects are closely entwined.

Moreover, while the researchers in both countries practice stem cell research within contrasting local and national regulatory regimes, our data suggests that they also transcend this local conditioning of research practices and social ethical discourses through a shared framing of the science, its objects and its prospective development. This redirects the gaze from the national regulatory context to the broader discursive shaping of research objects in the international dynamics of stem cell research.

Analyzing emergent objects

“Stem cell science” is a field that has drawn together different research domains from biology and medicine and is being constituted around both a proposed object (the stem cell) and a purpose (regenerative medicine). At present hES and iPS cells are uncertain objects, under negotiation, not crystallized technical objects (Rheinberger 1997). In order to account for their unstable character, we have taken a performative approach that explicitly addresses the formative quality of the construction of research objects in an emergent area of science and technology. Following an STS perspective, we understand the generation of scientific facts and artifacts as the result of both social negotiations (Barnes 1977, Bloor 1991, Barnes et al. 1996) and the contingent alignment of social and material processes (Latour 1987, 1999). In this sense scientific practice is performative, a reality forming engagement with the social and material world, seeking to capture and transform it (Pickering 1995).

The performative perspective in science studies is underwritten by a general conception of discursive practices that stresses their generative nature in the making of (social) reality (Austin 1962, Butler 1990, Foucault 2002). Scholars have shown how accounts of (future) scientific developments play a constitutive role in scientific practice, limiting and opening up certain options of interaction with the material world. Presentations of the current and envisaged science legitimize certain practices, enroll support from constituencies, reduce uncertainty and help to coordinate activities (Brown et al. 2000, Hedgecoe and Martin 2003, Borup et al. 2006).

In this article, we analyze the co-construction of scientific objects and pathways by examining scientists' accounts of hES and iPS cells. Our interviews were conducted at the time when the induction of pluripotency in ordinary cells had posed challenges to the established practices of stem cell science and more generally the linearity of biological development.

Following previous work on the rhetoric of pluripotency by one of the authors (Hauskeller 2002 and 2005), our empirical data demonstrates the complex ways in which scientists negotiate ethical challenges and societal expectations of future medical benefits in their construction of pluripotent stem cells. We illustrate how boundaries are drawn around these objects and how their biological, ethical and medical characteristics are co-constituted in a meaningful narrative of scientific development. The common narrative we identified from the interview data is performative in modeling stem cell research as a field of socially justified research and expertise, and in directing it as an emerging field of scientific investigation.

This analysis draws on observations and interviews with stem cell researchers working in Germany and in the UK. The two countries have contrasting regulations governing stem cell research.1 Drawing on accounts from researchers working in two different regulatory regimes has enabled our research group to examine the relationship between national regulatory contexts and the construction of research practices and objects (Wilson-Kovacs et al. 2010, Weber et al. 2011) and different national regulatory contexts of stem cell research have been studied in detail (e.g. Gottweis 2002, Hauskeller 2004, Schmidt et al. 2004, Bender et al. 2005, Campbell 2005, Jasanoff 2005, Prainsack et al. 2008). In contrast, little sociological research exists on researchers' constitution of stem cell research beyond national boundaries apart from analyses of practices of international standardization (Waldby and Mitchell 2006, Eriksson and Webster 2008, Stephens et al. 2008, Webster and Eriksson 2008). In this article we show how scientists integrate the emergence of iPS cells as new objects into a common framing of stem cell science and its objects. As a result, our article contributes to an analysis of the role played by the discursive shaping of stem cell science as a global effort that reaches beyond the national differences between the countries under study.

Method

This analysis is part of a broader comparative study of the social shaping of stem cell research in Germany and the UK conducted in 2007 and 2008. We carried out 10 weeks of ethnographic observations at four laboratories involved in hES cell research in both countries. Based on our observations we conducted in-depth interviews with senior scientists (heads of laboratories and research group leaders) and members of research teams at different career stages. The interviews covered stem cell science as a field of scientific practice and development, regulation, funding and collaboration. In order to broaden our findings beyond the local context of the laboratories we visited, we additionally interviewed seven heads of other laboratories engaged in hES cell research in both countries. We approached interviewees as active “conversational partners” (Rubin and Rubin 1995, p. 11) and encouraged them to expand on themes that they considered relevant. Here we draw on 24 interviews conducted in 2008.2 The data was analyzed using open coding on the basis of which themes were identified. These themes were further developed by means of examining the relationships within and between them using a constant comparative approach across participants and the two countries.

The Holy Grail

When in 1998 it was first published that cells had been isolated from four- to five-day-old human embryos in the laboratory and turned into cell lines (Shamblott et al. 1998, Thomson et al. 1998), this was presented as a scientific success with great therapeutic potential and celebrated by the journal Science as the “breakthrough of the year” (Vogel 1999). The “promise” was seen in one particular property of the cells, their pluripotency, taken to indicate their capacity to multiply indefinitely and to develop into any cell of the body. Within the vision of regenerative medicine, pluripotent stem cells might provide an unlimited source of tissues for the repair of damaged body parts and the cure of degenerative diseases.

Simultaneously, however, the derivation of the cells from human embryos triggered intense ethical debates over the dignity and protection of human life and led to the implementation of varied national regulations as to their use in research.

In studying cellular development, some scientists investigated alternative ways to make pluripotent cells. Pluripotency was interpreted as an early developmental stage to which the genomes of further differentiated human cells could possibly be reverted, or “reprogrammed” as it was termed in the information language common in genetics. In 2006 a research group in Japan found a way of producing pluripotent cells from mouse skin cells (i.e. cells of non-embryonic origin) through genetic modification (Takahashi and Yamanaka 2006). In November 2007, the same Japanese group and a US group, which had derived the first hES cells, succeeded in transferring the method to human cells, genetically reprogramming human skin cells into pluripotent stem cells, human iPS cells (Takahashi et al. 2007, Yu et al. 2007).

Apart from carrying the same essential characteristics as hES cells as regards their pluripotency, the first publications on iPS cells claim that they possess a further desirable characteristic, which is not an empirical characteristic in the usual scientific sense: while “ES cells remain controversial because their derivation involves the destruction of human pre-implantation embryos […] iPS cells remove this concern” (Yu et al. 2007, p. 1919). Thus, iPS cells, derived from adult human skin, not from human embryos, are seen as ethically less problematic. Moreover, both groups emphasize the relevance of these cells for future therapies. Identified as a “scientific and political breakthrough” in Science, the production of iPS cells has generated wide interest by scientists, the media and policymakers alike (Science 2007, p. 1844).

Our research was carried out shortly after the publication of these first papers and the laboratories we visited and the majority of senior scientists we interviewed had begun or were about to start experimenting on iPS cells. The technique of inducing pluripotency was framed as a major scientific advance. The nature of this major advance was seen to lie in three interlocking aspects: the ethical, biological and clinical characteristics of these cells. Our interviews show that scientists meaningfully co-construct the “ethical” nature of iPS cells, their biological and technical possibilities and the great therapeutic promise the simplicity of making these pluripotent cells may imply.

A postdoctoral researcher in the UK endorses the scientific achievement of iPS cells in the “by-passing [of] the ethical concerns with the embryonic stem cells” and continues, “I'm still trying to get my head round it sometimes. It's just that it's such a big leap forwards.” Similarly, a senior scientist describes the advantages of iPS cells:

Well, that one does not have these regulatory obstacles, that is an advantage. And yes, that one can start from any, that is from specific bodily cells and de-differentiate them and re-differentiate them again. (Senior scientist in Germany)

The advance constituted by iPS cells is connected to their clinical potential, i.e. the third aspect in the construction of these cells by a UK-based scientist:

Clearly it has the potential to overcome the ethical dilemma of using human embryos. It has the potential to make patient-specific cells in a way that might be better than using nuclear transfer. And … from a scientific curiosity point of view, it's quite a remarkable technology, it's quite remarkable that it works. (Senior scientist in the UK)

The fascination with the possibility of producing pluripotent cells from a skin cell relates to the fact that it undermines a long-held linear understanding of biological development. According to even recent theories in developmental biology, cells undergo a series of irreversible changes of their genomes in early development from being totipotent, to becoming pluripotent, then to becoming multipotent precursor cells of increasingly specialized tissues and finally becoming some or one of the 200 different cell types constituting the body (Hauskeller 2002, 2005, Cooper 2003). IPS cells unsettle this conception of biological development by opening up the developmental potential of cells to technical manipulation. By contrast, the researchers portray pluripotent hES cells as corresponding to a “natural” stage of organism development.

That the “reprogramming” of cells could be engineered had been shown in principle when in 1997 the sheep named “Dolly” was cloned via what is termed “cell nuclear replacement” (CNR), i.e. the transfer of an adult cell of a sheep into an enucleated sheep oocyte (Wilmut et al. 1997). The technique encouraged the vision of a future “regenerative medicine” and could potentially overcome one of the main barriers of transplantation medicine: the rejection of alien cells by the body's immune system. Through the cloning of human cells large amounts of pluripotent cells matching the genetic profile of a patient might be produced for tissue replacement or repair, thus combining the unrestricted capacity for regeneration ascribed to hES cells with the effortless maintenance of bodily integrity. However, CNR has equally been accompanied by deep ethical concerns. Research on the cloning of human embryos for the derivation of hES cell lines has been permitted in several countries including the UK, where it involves detailed approval procedures, while it has been outlawed in Germany.3 At the time of writing, no CNR cell lines have successfully been generated. This failure is attributed to both ethical and technical problems.4

Therefore, the fascination with the pluripotency of iPS cells that researchers convey does not merely center on the principle of reversing biological development, but is also concerned with the apparent ethical and technical simplicity of making them compared to CNR embryos:

I think that this development of these iPS-cells as technical possibility, is, let's say, simply a revolution in stem cell technology. It is basically the holy grail [German: “golden egg”] that people have searched for in the last 10 years in trying to basically clone embryos to derive patient-specific stem cells. That no one has shown until now that this actually works. And with these iPS cells there is [not] the whole problematic issue with cloning, the obstacle that one cannot get at an unlimited amount of oocytes. That the technique is incredibly expensive and laborsome. […] You can simply take any cell and make it into a stem cell. I think this is simply, let's say, a revolutionary step. It has also simply brought the applicability of stem cell technology for therapies at some point in the future a step closer. (Researcher in Germany)

In suggesting that one can “simply take any cell,” this researcher relates both the unproblematic supply of cells in terms of technical access – i.e. any bodily cell rather than a human oocyte, whose extraction is connected to a risky medical procedure – and ethical regulation. While access to body cells does involve approval procedures, these so far revolve around “informed consent” rather than entailing special regulatory oversight or even prohibition, as is the case when using human embryos or oocytes. In terms of laboratory techniques, the process of genetic modification used in simply taking a cell and making it into a stem cell is contrasted with the technical difficulties encountered in CNR research.

The quote exemplifies how the clinical characteristics of iPS cells, constituting the third aspect in scientists' construction of iPS cells, tie in with biological fascination and ethico-technical convenience. IPS cells are framed as providing an important step towards the development of medical therapies – the rationale that justifies stem cell research as biomedical endeavor. The researcher's reference to the production of “patient-specific” stem cells locates iPS cells within the vision of regenerative medicine to produce tissue transplants that resolve the problem of immune rejection of foreign tissue while overcoming the ethical and technical obstacles of CNR.

Most researchers refer to this vision of regenerative medicine in their description of iPS cells. However, cellular transplantation involving iPS cells is envisaged in a rather distant future. Scientists' views vary regarding the realization of its potential. This is partly because the cells had been genetically modified by means of a virus carrying four genes that were said to reprogram cells, at the time of our interviews. Viral vectors in gene therapy are known to carry increased health risks because they may cause unintended genetic mutations. Additionally, one of the factors then used in iPS cells is known to promote cancer. Since then, researchers have derived alternative techniques to induce pluripotency in cells, which are considered less risky (Okita et al. 2008, Soldner et al. 2009, Woltjen et al. 2009, Yu et al. 2009).

The potential use of iPS cells is also framed in terms of a more immediate future with regard to the creation of “disease-specific” cells for the study of diseases in vitro. As a “disease in a dish,” iPS cells may become used as models for drug screening and with this in mind, researchers elaborate a stepwise and open model of the application of iPS cells in medical research:5

That is of course a very exciting field […] that we can derive cell lines from patients and then try to investigate these cells in the Petri dish. That is a completely new field. Whereas the possibility to maybe develop therapies with these reprogrammed cells to then transplant these in regenerative approaches, is something which from my perspective is still so far ahead, that we are interested in the concept of pluripotency and what one can do in terms of disease models. (Senior scientist in Germany)

There might be new toxicity tests and new drug discovery tests or some medical applications. Even though I think they are further away than drug testing, which can help then people who get maybe faster, better medication or they find that, “oh this is a toxicant which shouldn't be any more in the production line somewhere.” So people will benefit from it by getting maybe less diseases or better medication or a new treatment. (UK-based researcher)

The interviewees describe iPS cells as a “leap forwards,” “a revolution” or “the holy grail's almost there” (UK-based postdoc). It is the combination of biological, ethical, and medical properties of the iPS cells that establishes their potential as novel research objects. The intimate entanglement of these properties in the scientists' accounts demonstrates that scientists actively co-constitute their research objects within the scientific and social parameters of stem cell research as a promising and contested field. In developing a stepwise model of future therapeutic applications these researchers remain cautious and some make critical remarks about the “hype” and that iPS cell research has become “fashionable.” In addition to the potential of iPS cells, researchers also emphasize the necessity for continued research on hES cells.

The “gold standard”

The scientists working in Germany and the UK accord iPS cells a special significance; at the same time, they also problematize their status as uncertain objects. This uncertainty is used to legitimize the continued use of the ethically controversial hES cells. They see “the big danger that people say, ‘oh, […] you're not allowed to work with ES cells any more, ‘cause you don't need them’” (UK-based senior scientist). A colleague in the UK expands:

I think the induced pluripotent stem cells over the last two years have really, kind of created quite a significant impact in the field, because people had been working quite hard with human embryonic stem cells, but now with the induced pluripotent cells where you take an adult cell and reprogram it to an embryonic stem cell state, that removes all the ethical concerns … or largely removes the ethical concerns. And so, people see that perhaps as a better route to cells for therapy, etc., than the ES cell route. But I think that most people agree that those two tracks need to go along in parallel, because the induced pluripotent cells, there's so many things we don't know and how [much] really like embryonic cells are they? (UK-based senior scientist)

This account illustrates a dual operation, which we also found in other accounts. The significance of iPS cells is constructed around the fact that their potential is the same as hES cells as regards their pluripotency. Yet, in arguing that research on iPS and hES cells must evolve in parallel, they are also framed as different in that little is known about their status vis-à-vis hES cells. Implicitly, hES cells are presented as having a stable status as scientific objects against which the properties of iPS cells can be measured and determined, as a UK-based postdoctoral researcher expands:

[…] the embryonic stem cell is your primitive cell, it is your blueprint cell. Your induced pluripotent stem cell has differentiated into a differentiated cell, i.e. your skin cell and has then been forced backward to a pluripotent stem cell-like state. So there will be differences between the two. Whether those differences will bear out actually in functionality, I'm not sure. (UK-based postdoctoral researcher)

The reference to the hES cell as a “blueprint cell” or as other scientists put it the “gold standard” in part expresses the logic of experimental control and comparison in the life sciences. However, the description of the hES cell as a “primitive” cell points towards a further dimension in the constitution of hES cells as the relevant comparator for iPS cells. A UK-based senior scientist explains:

No matter what you're going to do with iPS cells, you need to know something about them, what they are and how they relate to other cells in the body and I think the crucial cell in this respect is the cell of the very early embryo, which can make everything. So I think this is why hES cells are the sort of gold standard. […] they're the normal cells that can make everything in the body. (UK-based senior scientist)

Similarly, a senior scientist in Germany comments:

The individual develops from the embryonic stem cell. That is the normal biological process. From this one can assume, that it can do everything, because this is what always happens in the natural environment. The difficulty here then does not lie in establishing whether this cell can do everything – one can presume that – but rather in whether one can provide the appropriate micro-environment, so that it also functions in the Petri dish outside of its normal development in-utero. (Senior scientist in Germany)

These accounts convey three important notions that characterize hES cells in relation to iPS cells: (a) hES cells are portrayed as established objects of research practice, especially suited as models for experimental control; (b) hES cells become the “normal” pluripotent stem cells. This normalization takes place within the linear model of development that takes the hES cell as representing an early stage of differentiation from which all latter cell types derive and which is defined by “natural” pluripotency; (c) the pluripotency of iPS cells as the product of genetic intervention in the laboratory is implicitly presented as not natural, an artificially produced property. This pluripotency of iPS cells needs to be checked against the “normal” pluripotency of hES cells. This normalization reduces the complexity of the hES cells, which is arguably also the product of technical intervention and laboratory culturing practices. A researcher problematizes hES cells as “gold standard”:

They are definitely very early cells. And that is why they are something like a gold standard. Although one also needs to be a bit cautious about that. This is all more difficult. One cannot just reduce this.

He further explains:

Stem cell line A does not equal stem cell line B. Their characteristics are different. If one were to look in Harvard, they made 17 stem cell lines, […] some […] simply prefer to become one cell type. The others another cell type, and so on. This means nothing there is the same. And that is why one cannot really speak of a gold standard. (Researcher in Germany)

While this researcher's account draws on his daily experiences with the variability of live research objects and the frustrations of controlling and making sense of them in a laboratory setting, debates about the status of hES cells have been ongoing since such cells were first created in 1998. Are they “culture artifacts” merely reflecting particular culturing conditions in the laboratory, rather than natural entities? Which developmental stage do they correspond to if they “recapture” the development of embryoblast cells in vivo (Zwaka and Thomson 2005, Brons et al. 2007, Tesar et al. 2007, Bhatia 2008)? Additionally, the biological criteria and culturing practices for establishing the pluripotency of hES cell lines have been subject to collective negotiations as part of efforts to standardize hES cells as research objects (Adewumi et al. 2007, Eriksson and Webster 2008). This illustrates that the epistemic status of hES cells as “original” cells has not been stable at the heart of hES cell research.

Rendering hES cells as the necessary “gold standard” of managing pluripotency in the laboratory brackets this instability. This framing of hES cells in relation to iPS cells shows how in enacting particular research trajectories vis-à-vis different audiences, the interviewees meaningfully condense or elaborate the uncertainties of their research objects (Brown and Michael 2003). In the co-constitution of iPS and hES cells, the normalization of hES cells makes them the ontologically prior object of knowledge. This ontological priority counteracts the ethically precarious status of hES cells by establishing them as the necessary referent in the study of pluripotency.

Concomitantly, some researchers highlight their longstanding experience with and in-depth knowledge of culturing and experimenting on hES cells. These accounts also render hES cell researchers as a privileged epistemic group in the study of iPS cells and present iPS cells as a direct follow-on from hES cell research:

[…] if you look at the guys who've been making iPS cells, who are they? They're, with the exception of Yamanaka, they're all stem cells guys; George Daley, Jamie Thomson, Doug Melton, some guys out in California, they're all people who came from hES cells, because you still need to know how to grow cells. (UK-based senior scientist)

Well, I do not designate iPS research as adult stem cell research, […] it is actually pure embryonic stem cell research. Even if these are adult cells that have been reprogrammed, but one basically utilizes embryonic processes. […] It is not a miracle that the people who developed induced pluripotent stem cell-technologies are well-funded, very good, intelligent, basic embryonic stem cell researchers. (Senior scientist in Germany)

This framing of the development of iPS cells stresses that “adult” stem cell researchers could not have produced them and entails, we suggest, a claim for epistemic authority over iPS cells. In policy debates, especially in Germany, adult stem cell research has been identified by many as the way forward for an ethically non-controversial stem cell science and iPS cells were endorsed as non-embryonic stem cells. In shifting iPS cells into the realm of hES cell research, the role of past and future adult stem cell research in the constitution of these cells is denigrated. Rather, a continuous identity between hES and iPS cell research is established whereby the former appears as the historical condition for the generation of the latter and hES researchers as experts for developing their potential.

Implicit in the understanding of hES cells as the “gold standard” of pluripotency is a notion according to which iPS cells have a less certain identity that must be explored alongside further hES cell research. This also legitimizes hES cell research against critics who request its discontinuation following the generation of iPS cells. In claiming scientific authority over iPS cells, our interviewees present hES cell researchers as key agents in the realization of the scientific and ethical potential of iPS cells.

The shaping of stem cell science

The reported understanding of pluripotent cells among hES cell researchers shows the complex framing of the ethical and scientific properties of research objects in stem cell science. Stem cell research has become the subject of an international bioethics discourse that has been constituted principally around the ethical classification of the different sources of stem cells and the techniques of manipulating them (Salter and Salter 2007). Based on a linear notion of human development, in this discourse, the human embryo has been imbued with a special moral status because of its potential to develop into a person. Accordingly, ethical controversies have centered on whether the use of human embryos for the derivation of hES cells contravenes principles of the protection of human life and its dignity. In most legislations hES cells are rendered as legitimate, albeit contested, objects of biomedical science. Thus, a “protected” if precarious space has been constituted around stem cell research (Hoogma 2000), the safeguarding of which requires continued efforts by scientists and commercial investors to legitimize their practices vis-à-vis regulatory agencies, various publics and stakeholders (Franklin 2003).

Our analysis of the performative accounts of the scientists shows that stem cell researchers in Germany and the UK situate themselves within this protected space. The generation of pluripotent stem cells from adult cells, which have been considered as an unproblematic source, potentially threatens the fragile legitimacy of hES cell research. Policymakers, religious and other groups opposed to hES cell research have argued that iPS cells represent an alternative to hES cells and cloning techniques rendering them obsolete.⁷ In defending their work, researchers engage in a complex rhetoric: they simultaneously present iPS cells as a “breakthrough” and justify the continuation of research on hES cells as necessary. This involves a twofold process of co-constitution.

First, in addressing ethical evaluations of the cells and future therapeutic developments, researchers intimately connect the biological, ethical and medical features of the cells. This is expressed in the way in which the “revolutionary” potential of iPS cells is defined: it is constituted both by the biological reconfiguration of the limits of cellular development and by the ethical and technical convenience involved in making pluripotent cells. Moreover, iPS cells are accorded a special role in the vision of regenerative medicine allowing for the creation of patient-specific cells that avoid the ethical and technical difficulties of CNR. However, this potential of iPS cells can only be realized on the basis of their comparison with and the continuation of research on hES cells, whose presentation as an ontologically prior, “normal” standard of pluripotency offsets their ethically contested status.

Secondly, the co-constitution of pluripotent cells is defined by a narrative as part of which scientists present a particular research trajectory for pluripotent stem cell research. IPS and hES cells are aligned in a linear temporal pattern whereby hES cells as “gold standard” become the established research objects that form the historical condition for the generation of iPS cells. Thus a temporal continuity between iPS cells and hES cells is established, which renders hES cell research indispensable for the study of iPS cells, as uncertain objects. The allocation of differing temporal registers to hES and iPS cells involves the meaningful management of scientific uncertainty, as part of which the continuing uncertainties of hES cells are backgrounded. As a result, research on iPS cells is portrayed as an important step in scientific development, which addresses pre-existing ethical concerns and societal expectations of medical benefits. The narrative maintains the vision of regenerative medicine as a long-term (if uncertain) goal and presents a more immediate utility of these cells as models in drug development and disease treatment. In cautioning against the novelty of iPS cells over and against the tried and tested hES cells, the researchers present themselves as prudent agents engaged in the responsible pursuit of the science and its future medical applications (Michael and Wainwright 2005, Wainwright et al. 2009).

Conclusion

Scientists' construction of pluripotent stem cells demonstrates the elaborate formation of research objects, which reflexively integrates the scientists' conception of the discourses of other societal actors including politicians, funding institutions and publics. The narrative of the scientific development of hES and iPS cell research performs a particular research trajectory as part of which scientists' research practices can be rendered ethically informed, socially meaningful and sound as science. In setting pluripotent stem cells within a meaningful context of past and future developments, this narrative serves to actively model the “protected space” of stem cell research following the emergence of iPS cells by seeking to secure hES scientists' research practices in the present and to discursively stabilize pluripotent stem cell research as a field marked by ethical and scientific uncertainty.

Our finding of this shared research trajectory, as part of which researchers in the UK and Germany present their research objects, provides an additional dimension to the examination of (national) science policy arenas that so far have been at the center of social scientific research on stem cell science. These analyses have elucidated the cultural differences on the basis of which legitimate research objects are constructed and regulated. As a result, they have tended to black box the simultaneous international dynamics within which stem cell research proceeds as global science.

By contrast, our data elucidates the coexistence of two mutually informing approaches that shape stem cell research. Our interviewees in Germany and the UK elaborate their research practices within differing local and national contexts that have a considerable impact on which objects they can investigate and how they go about doing so. However, they also engage in a common discursive framing of pluripotent stem cells. This framing disentangles them from local orders of daily scientific practice and their regulatory specificities. STS scholars have shown that new technologies depend upon the mediation between such local orders and global orders, which emerge through processes of abstraction and aggregation of local practices (Disco and van der Meulen 1998). In the stem cell field these include standardization practices as carried out by the International Stem Cell Initiative or the formation of global actors such as stem cell banks and stakeholder organizations such as the International Society for Stem Cell Research (Waldby and Mitchell 2006, Adewumi et al. 2007, Stephens et al. 2008, Webster and Eriksson 2008). Additionally, we suggest, these global orders are constituted through “global discursive repertoires,” as indicated by the shared construction of iPS and hES cells by researchers in Germany and the UK. These are formed as part of international networks of knowledge exchange and the broader bioethics discourse. This ethics discourse involves the definition of legitimate research objects, using and distinguishing categories of contestation (human embryos, hES cells, legitimate modes of manipulation), and narratives of scientific progress and therapeutic promise.

As part of the mediation of local and global levels, this shared construction of pluripotent cells may in turn feed into the national constitution of research practices. Both the UK and German national legislative frameworks were undergoing changes at the time when the generation of iPS cells was reported. In Germany, the creation date of the stem cell lines which scientists could apply for to use in research (cut-off date) had been moved from 1 January 2002 to 1 May 2007, and with it the number of hES cell lines that may be imported has increased, while human embryo research remains prohibited. In the UK, the range of legitimate research objects has been extended. It now includes human-animal embryos, so-called admixed embryos. In the policy debates preceding these changes, proponents of loosening regulatory control of research in both countries drew on the common framing of hES and iPS cells in legitimating regulatory changes against other stakeholders that enlisted the “ethical” provenance of iPS cells to oppose them (e.g. Bundesverband Lebensrecht 2008, Passion for Life 2008).

There is no room here for a detailed analysis of the contrasting ways in which (pre-existing) structures of ethical reasoning and managing scientific uncertainty have shaped the recent legislative debates and the scope of legitimate research practices in national and international scientific and regulatory contexts. Our analysis demonstrates, though, that for a deeper understanding of the dynamics of stem cell research as an emergent field of biomedical science, comparative ethnographic research is especially illuminating, because it can address the diverse ways in which local, national and global practices of framing stem cell research intersect. In the context of the new pluripotent iPS cells their common framing by scientists in both countries legitimizes the continuation of hES cell research and the utility of the expertise of its practitioners. The shared narrative also serves to performatively lift the science beyond national ethical or regulatory particularities to claim global validity for its objects and practices.

Acknowledgements

The support of the Economic and Social Research Council (ESRC) is gratefully acknowledged. The work was part of the research program of the ESRC Centre for Genomics in Society (EGENIS), funded by an ESRC Stem Cell Social Science Initiative Grant (RES-329-25-0002). We thank the participants in this study for generously giving their time and our colleague Dana Wilson-Kovacs for discussions of the themes and comments on this article. We also benefited from helpful comments by Barry Barnes and Sabina Leonelli on a draft version of the paper. The responsibility for the contents of this paper lies with the authors.

Additional information

Notes on contributors

Christine Hauskeller

Both authors contributed equally to the writing of this paper.

Susanne Weber

Both authors contributed equally to the writing of this paper.

Notes

Germany prohibits research on human embryos and only permits researchers to import hES cell lines that were generated before a particular cut-off date (moved from 1 January 2002 to 1 May 2007 as part of legislative changes in 2008) after ethics approval for each individual study. The UK allows research on pre-implantation embryos including the derivation of stem cell lines and has generally expressed a favorable commitment to developing stem cell science (Hauskeller 2004).

The interviews were recorded, transcribed and where applicable translated into English.

The concern was that the cloning technique could be used to clone human beings. Its potential application in human reproduction has been banned in a UN resolution (UNGA 2005).

Developing cloning requires large numbers of human oocytes. Access to human eggs presupposes interference with a woman's reproductive cycle. Ethical and medical concerns have been raised regarding the hormonal treatment of women for the purpose of egg donation and the potential commercialization of women's bodies (Arditti et al. 1984, Corea 1986, Waldby 2008). The fusion of ES cells with grown cells has constituted another so far unsuccessful attempt to produce patient-specific cells (Cowan et al. 2005).

Using cell lines in pharmaceutical development has also been envisaged for hES cell lines (McNeish 2004).