Abstract
In this chapter, the focus is turned from the hypothetical and anticipatory perspective of stem cell-based clinical translation to the “realities” of laboratory life with human pluripotent stem cells. Here practical challenges of instrumentalizing the artificially created iPS cell lines and their volatile and fickle vitality become poignant. The chapter describes the discovery of the revolutionary method of cellular reprogramming, followed by the analyses on what is required of biomedical craftwork to make use of the new biological tool and how this work is conditioned by and dependent on the bourgeoning life science industry. Theorizing laboratory labor through pragmatist discussion on craftwork, the chapter shows that biomedical research is essentially an embodied craft and the skill of cellular reprogramming begins as bodily practices.
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Notes
- 1.
I have chosen to keep with the idea of constitutive relationality proposed by Haraway for the sake of conceptual clarity. However, constitutive relations between humans and nonhumans have been deliberated in many ways in the field of STS and feminist science studies in particular, and I acknowledge that the discussion in this chapter could be framed also in relation to Karen Barad’s conceptual work on humans, technologies, and science. Like much of Haraway’s work, Barad’s theory on intra-action aims to advance the philosophical premise that “humans enter not fully formed, preexisting subjects but as subjects intra-actively co-constituted through the material-discursive practices that they engage in” (Barad 2007, p. 168). Furthermore, Barad thinks that agency does not reside in humans only nor aligns mainly with intentionality or subjectivity (see also Chap. 1).
- 2.
When inserted into the cell with the help of viral vectors, the reprogramming genes initiate a transcription network in the inner cell mass that is essential for pluripotency. The inserted genes bind to so-called target genes in the DNA which have a role in either upregulating pluripotency or downregulating lineage commitment. This commences a transcriptional regulatory network, thereby controlling the flow of genetic information from DNA to messenger RNA concerning pluripotency and differentiation (Babu et al. 2004; Gilbert 2010; Mikkola 2012).
- 3.
I am aware of the problematic of depicting the first findings on iPS cells in such a concise way, suggesting a linear and “unmessy” story of research developments within the field of stem cell science. If we take the lessons of STS seriously, the emergence of the new tool cannot be such a tidy process. My access to the initial making of the iPS cells and the reprogramming method is however limited to scientific publications, which tell the history of scientific discovery in a rather restricted way, omitting much of the wider constellations of, for example, cultural and political interests. Later in the chapter I will hopefully be able to pluralize the view on the emergence of the iPS cell technology with the accounts and experiences from laboratories trying to make the tool work. Nevertheless, a detailed sociohistory of the iPS cell technology remains to be written, where “various constituencies” (Jordan and Lynch 1998) associated with the technology could be traced, including the local and global efforts to “find” the way to reprogram cells and to outperform others in this competition.
- 4.
The ability of a particular stem cell to generate numerous different types of differentiated cells is its potency. Cells are classified according to the grade of their potency from totipotent to pluri- and multipotent to more limited differentiation potential (Gilbert 2010). Pluripotent stem cells can both renew themselves and become all the cell types that are found in an implanted embryo, fetus, or developed organism. IPS cells have been classified as one of five pluripotent stem cell types that have been characterized thus far. The other four are embryonic carcinoma cells, embryonic germ cells, embryonic stem cells, and adult testis-derived germline stem cells (Mikkola 2012). The category of pluripotency, however, is a sustained topic of discussion in the field of stem cell research since it has been used as a vital demarcation criterion separating the embryonic stem cell research from somatic or adult stem cell research. Research has shown that the criteria of pluripotency are not given but rather constantly challenged with the interplay of new biological knowledge, practical expertise, and ethical and legal debates (e.g. Eriksson and Webster 2008; Hogle 2010; Meskus and de Miguel Beriain 2013).
- 5.
In the case of stem cell tools, and from the perspective of scientific craftwork, the distinction between the creation and use of the tool is problematic and even misleading as both phases involve substantial genetic manipulation and similar challenges of cell culture and maintenance. It must be emphasized, however, that I focus on the local generation of the tool while leaving out of the picture the subsequent uses of iPS cell lines in generating differentiated patient-specific cell lines, such as neuronal, cardiac or pancreatic cell lines. During the early years of the iPS cell technology, research laboratories I visited were still struggling in generating fully characterized, functional and caryotypically normal iPS cell lines. Thus, my analysis is centered more on the situated creation of the novel cellular tool than its further uses in differentiation experiments.
- 6.
Scientific work on stem cells requires so-called healthy wild-type control cells, in order to conduct comparisons with the created disease-specific cell lines (e.g. Saha and Jaenisch 2009).
- 7.
Only those lines, which work in the experiments, are reported in scientific papers, indicating the phenomenon of data bias in research publications. This problem does not pertain only to stem cells science, but is rather a common feature in scientific publishing. According to John P. Ioannidis’s (2005) famously critical analysis of the publication system, it stems from the fallacy of viewing negative data or failures to replicate experiments as uninteresting or harmful pieces of information (see Meskus et al. 2017).
- 8.
In Epistemic Cultures (2000, pp. 283–285) Karin Knorr Cetina reports a discussion she had with an artist-philosopher on the anthropomorphic classifications she noted in her study on experimental high energy physics. I confess having experienced similar frustration as Knorr Cetina does in the face of arguments that humanizing and personifying characterizations of nonhumans are “merely” a sign of anthropomorphization. These arguments often relate to anthropomorphism having become a sign of unscientific approach (Horowitz 2007). I agree with Knorr Cetina that the term does not itself explain anything and that the phenomenon cannot be explained away as being “just” that. Knorr Cetina tackles the question by emphasizing anthropomorphic classifications as systematic patterns of scientists relating to their objects in situations where technical vocabulary turns out narrow and inadequate. My line of analysis does not focus on the vocabulary as such but on the embodied relations stem cell science as a field of practice produces and demands. Writing about human-animal relationships and empirical testing of anthropomorphisms, Alexandra Horowitz (2007) notes that it is often professional observers of animals, who with exposure and despite their training are more likely to anthropomorphize. Turning to cells and the history of tissue culture, Hannah Landecker (2009) shows that personification of cell lines as well as endowing individualized identity and intentional action to cell-level phenomena has been a visible tendency in the scientific literature. Landecker argues that it should not be dismissed as simplification for the purposes of popularization. Rather, it is part of the scientists’ relation to the material they are working with, however biased the descriptions may be. Agreeing with this interpretation I suggest that in the case if iPS cell culture, anthropomorphizing accounts of cell behavior underscore the point about the variable vitality of the research material. IPS cell populations produced in the lab are substantially manipulated living material the vitality of which researchers experience as full of character.
- 9.
I attempted to get the right to reprint the figure from Lonza. For a few weeks, it looked as if the permission would be granted; however, before the final signing of the permission request form, the product manager in charge and the company legal department wanted to review the text section I was intending to illustrate with the image. Unfortunately, they decided to withdraw the permission but kindly offered a detailed reason for the decision, which is informative to disclose here. The e-mail I received stated that while the Lonza personnel agreed with my “underlying premise that research progress is not in the long term benefited by shortcuts”, they argued that this premise is not “universal” in the sense that “Lonza can and does provide valuable products/services that speed up research progress without impacting scientific growth through experience”. The response further reads, “there is absolutely high value for beginning grad students/post docs, or any investigator starting in a new research area to ‘explore the maze’ as you suggest. But once past that early learning and understanding stage (e.g. iPSC generation/differentiation), it does make sense to utilize the broader life science community and take advantage of specialized expertise and products.” Therefore, it was felt in the company that, even if perhaps inadvertently, the way I was intending to use the image would “potentially reflect negatively on our brand and products” (e-mail exchange with Lonza marketing communications department, 26 June 2017). Although I do not find my analysis significantly different or conflictual to Lonza’s interpretation , I agree with the company’s view that the effect of using ready-made products in developing researchers skills and getting experienced with a new technology changes with time and practice gained. However, this does not omit the general dilemma of learning by experience in biomedical research, which emerges through hands-on experiments with the living cellular material. As biomedical research is increasingly embedded in and dependent on the life science industry also in the labor-intensive field of stem cell science, the enabling and disabling effects of this development need to be studied further.
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Meskus, M. (2018). Making iPS Cells in the Laboratory. In: Craft in Biomedical Research. Palgrave Macmillan, New York. https://doi.org/10.1057/978-1-137-46910-6_4
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