Constructing Objects and Transforming Experimental Systems Juha Tuunainen

University of Helsinki

The main contribution of this paper for social studies of scientiªc practice is to use and further elaborate the concept of experimental system. It is expanded from mere epistemic concerns to also incorporate the built-in practicality and societal relevance of scientiªc research. For this, an analysis of object construction by a potato-biotechnology research group is presented. The group’s object of activity is conceptualized as a dual one comprising both the epistemic and applied objectives. The application object points to the virus-resistant cultivated potato under construction, the epistemic object to the knowledge on the virus-resistance mechanism. Two major phases of the group’s work are perceived as distinct experimental systems. The transition between them is analysed in terms of a gradual evolution characterised by network collaboration, ad hoc improvization, resistance, opportunism and informal interaction. 1. Introduction

Scientiªc practice has been approached from multiple theoretical perspectives. This paper will investigate the relevance of the concept of experimental system as a theoretical tool to analyse laboratory work. My aim is also to develop that concept further. I shall argue that, as it now stands, the experimental system remains too internalistic: it is strong in addressing the epistemic concerns of scientiªc practice but fails to incorporate into its realm the built-in practicality and societal relevance of research. With special reference to a case study and the notion of object of activity I am grateful to Mervi Hasu, Sampsa Hyysalo, Marja Häyrinen-Alestalo, Janne Lehenkari, Reijo Miettinen, Eija Pehu, Veli-Matti Rokka, Laura Seppänen, Lucy Suchman, Jari Valkonen, Milton Zaitlin, and the two anonymous referees from this journal for their invaluable comments and critical review of the earlier versions of this paper. I also thank Marjatta Zenkowicz for the thoughtful linguistic revision. Funding of the projects Technical Innovations and Organisation of Research Work (no. 37370) and Changing University Research and Creative Research Environments (no. 49789) by the Academy of Finland is thankfully acknowledged (Finnish Centre of Excellence Programme 2000–2005). Perspectives on Science 2001, vol. 9, no. 1 ©2002 by The Massachusetts Institute of Technology 78

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derived from the cultural-historical activity theory, I shall delineate a way to overcome this shortcoming. Before entering into the theoretical argument, I shall brieºy introduce my case. The Pehu plant-biotechnology research group was founded at the Department of Plant Production, University of Helsinki, Finland, in 1990. Its aim was to combat the biological hazards created by viruses in potato production by means of producing a virus-resistant potato. The progress of the group’s research programme falls into three partially overlapping phases: In the ªrst phase (1990–96), the group studied virus resistance in potato, attempting to transfer a natural resistance trait from a wild-potato species to the cultivated potato. The second phase (1993–96) saw the development of genetic engineering methods, by virtue of which the potato-virus genome could be used as a source of virus resistance. In the third phase (1997–2000), these new methods were worked on further to derive commercially exploitable products. Each of the phases was characterised by the group’s attempt to develop the virus-resistant potato and to understand the underlying plant pathology. Although the ultimate motive for the research remained much the same during the whole process, the scientiªc concepts and methods underwent radical alteration. A major transformation in this respect occurred between the ªrst and second phases at the emergence of a new research approach within the group. Questions, thus, arise: How and why did the alteration happen in the ªrst place? What was the relationship between scientiªc research and application? And what kind of conceptualisation would be useful in tracing and understanding that transition? In the following, I shall investigate these questions by making use of the concept of experimental system. My application of it is critical: my aim is both to test its usefulness as an analytical device and to contribute to its further development. The case presented is not a deep ethnography of practices in a local laboratory. Instead, it is a recent history of experimental work done by a group of researchers, an account that has been retrospectively reconstructed on the basis of interviews, publications, and documents. By interconnecting these data and comparing them, I have traced the development of the research programme. Between 1997–2000, I interviewed nearly all the members of the group, an administrator of a Finnish science-funding agency and two senior plant biologists from major United States universities. The total number of analysed interviews with 9 people added up to 13. In these discussions, the researchers were set to tell about the details of their work practices quite freely. Typically, the interviews lasted for an hour and a half. Almost all of the group’s research proposals, reports and publications pertaining to the virus-resistance studies were consulted, as

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well as other relevant materials at hand. During the research process, different versions of the manuscript were subjected to validation and revision by those interviewed and studied. The experimental system set forth in this paper is peculiar in concentrating mostly on the technical and material aspects of experiments. The social dimension, except for the network collaboration, is described in a much lesser degree. This is done for three interrelated reasons: First, because the studied group was a new-born community, the researchers travelled a lot and worked for long periods of time in other laboratories; only a limited amount of direct interaction between them was possible in their home base. Second, owing to the relatively small amount of collaboration between the group members, many of the interviews comprised the descriptions of the researchers’ personal projects, their technical detail, and how they related to the collaboration networks of the scientists. And third, since the appropriation of new materials, tools, and techniques via networks seemed to form such a central feature, I urged the scientists to tell about those in the interviews. 2. Studying Scientiªc Practice: The Concept of Experimental System Redeªned

Reviewing the theoretical developments in the ªeld of science studies since the late 1970s, Andrew Pickering concluded that the sociology of scientiªc knowledge “simply does not offer us the conceptual apparatus needed to catch up the richness of the doing of science” (Pickering 1992, p. 5). Thus, new concepts are needed. From my point of view, an experimental system is among the most promising candidates. Multiple researchers have used that concept to characterise the dynamics of contemporary experimental science. Hans-Jörg Rheinberger has provided the most recent and theoretically most elaborated deªnition. He regards experimental systems as “the smallest integral working units of research” that are designed to create new phenomena and knowledge (Rheinberger 1997, p. 28). Theoretically, he discerns two types of elements in them. He calls the ªrst a scientiªc object, or an “epistemic thing.” An epistemic thing is “that material entity which is the object of manipulation” (Rheinberger 1995, p. 110). During the research process scientiªc objects continually make their appearance and become successively redeªned in changing experimental contexts. These contexts form the second element of the experimental systems, and Rheinberger calls them technical conditions, or “technical things” (Rheinberger 1997, pp. 28–31). They are materials and methods of experiments that “determine the space and realm of representation of an epistemic thing” (Rheinberger 1995, p. 111).

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In case-history studies the concept is used more loosely. In these studies, experimental systems typically consist of heterogeneous elements, such as groups of researchers and their networks, model organisms, aggregates of equipment, techniques and methods, research materials, concepts and assumptions (Turnbull and Stokes 1990; Kohler 1994; Rheinberger 1994; Keating and Cambrosio 1997). Understood in this way, the experimental system becomes a parallel to the concept of an activity system (Leont’ev 1978; Leontyev 1981; Engeström 1993; Cole and Engeström 1993), or the mangle of practice (Pickering 1995). My aim in this paper, however, is to further develop the concept of the experimental system. To begin with, my criticism of the concept is that it is essentially internalistic. The power of the experimental system lies in its bringing to the analyst’s attention epistemic objects and an abundance of instruments, methods, tools and hypotheses in a way that is neither predetermined nor entirely unorganised. At the same time, however, it fails to offer tools to conceptualise experiments in their larger societal contexts. Experimental systems are revealed as if they were invented, developed and used only for the purpose of creating new knowledge. Looking at them as such is vital, of course, but the experimental system should also be capable of including the practical concerns of scientists, that is, the “dual focus” of researchers on both fundamental science and societal utilisation of research results (Kleinman 1998a; Miettinen 1998).1 In the present case, such concerns were inherently built into the research programme, although the group had not yet entered into close collaboration with practitioners or industries. To account for such a dual nature and to theoretically further develop the experimental system, I shall introduce the object-of-activity concept developed within cultural-historical activity theory. Basically, Rheinberger’s notion of epistemic thing is compatible with the concept of object in that both offer a way to overcome the dualism of ideal and material in experimental practice. In the case of the experimental system, the material production of difference in time results in multiple representations oscillating around an epistemic thing. In activity theory, the collective human activity is considered being oriented towards an object. The object denotes, simultaneously, both the motive of human activity, the ªnal use-value of the products of work in the society, and its raw materials undergoing constant construction and transformation. As formulated by Yrjö Engeström (2000, p. 156), the object of activity is pro1. Also Knorr-Cetina (1982) addressed this feature when speaking about “transepistemic connections of research.” In general, plant biotechnology seems to be a good example of such connections, see Bud (1991), Joly and de Looze (1996), and Kleinman (1998b).

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jected and anticipated by human subjects, hence, a project that is “moving from ‘raw material’ to a meaningful shape and to a result or an outcome.”2 This diminishes in no way the materiality of the object in which both dimensions exist concurrently and interactively: material entities are made objects by imagining, hypothesising, perceiving, and acting on them (Engeström 1990, p. 107). Thus, the activity theoretical contribution to the analysis of experimental systems lies in the ability to account for the societal motives built into the object of research work. The realm of the epistemic thing is expanded into a truly social object incorporating both the epistemic and the applied dimensions of the research results. This duality is derived from two interconnected agendas: (1) an attempt to create new theoretical knowledge and models published in scientiªc papers (epistemic object) and (2) an aim to construct outcomes that have practical value in some other sphere of societal activity than science (application object) (Miettinen 1998; Saari and Miettinen 2001). The proposed dual nature of the object clearly exceeds the limits of Rheinberger’s conception of an experimental system. I shall make use of that extension to incorporate the application object into the analysis of epistemic things. In my case, the application object comprised the construction of the virus-resistant potato and its envisioned use in agricultural production, and the epistemic object scientiªc knowledge on virus resistance. Given the two distinctive but overlapping phases of the research programme, two different yet interconnected experimental systems are identiªed: the wild-potato system and the viral-gene system.3 Both of these systems (and their various versions) were dependent on the group’s 2. Laboratory studies typically addressed the object construction process in terms of constructing a scientiªc fact (e.g., Latour and Woolgar 1979). Later, Knorr-Cetina (1999, p. 37) spoke about natural objects “as processing materials and as transitory object-states corresponding to no more than a temporary pause in a series of transformations.” According to activity theory, the object of activity is two-fold: On one hand, it exists independently in the environment and is selected by subjects to be the object of construction and transformation. On the other hand, it is a future image of the object to be constructed. The object includes raw materials, which are transformed socially, mentally, and materially into outcomes or products by the human activity. As a result, it becomes objectiªed into a hybrid system with physical, biological and human elements (Miettinen 1998). 3. The task of deªning an experimental system is a complex one. The boundaries between the systems are not clear-cut, and multiple systems may occupy overlapping areas of investigation. In the data, the experimental systems “appeared” in the form of the technical vocabulary of the research approaches developed and used by the researchers. The technical talk about the experimental systems designated research materials, tools, methods, results and ideas, as well as a particular series of experiments. Occasionally, the term “model system” was used to designate the outcome of the research, the virus-resistant cul-

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collaboration networks: access to tools, methods, and ideas indispensable for object construction was secured only through the social networks mobilized in different phases of the research work. As a consequence, the experimental systems exceeded the boundaries of single laboratories while being, all at once, local accomplishments. The following Table illustrates my conceptual redeªnition of the experimental system with reference to the particularities of the case. With the concept, I am designating the two alternative assemblies of raw materials, tools, methods, ideas and hypotheses utilised by the group in the work of constructing the object of activity. In Table 1, three dimensions of the experimental system are summarised. First, Rheinberger’s epistemic thing is extended to incorporate the application object as well. Second, the working hypothesis of the virus-resistance mechanism to be constructed and used in the work of creating the virus-resistant potato is speciªed. And third, the technical things are changed into a more telling idiom that differentiates between fundamental research materials, tools, devices and methods. As summarised in Table 1, the motive and the object of the research activity remained the same in the two experimental systems. The research materials, tools, devices, and methods, as well as working hypotheses, however, differentiated radically. Given the two distinct sources of virus resistance, the corresponding hypotheses of the utilisable resistance mechanism4 varied. Based on them, the group attempted to construct an agriculturally useful experimental effect (Hacking 1983), a potato that could resist viral infections out in the ªelds. In this paper, I shall follow the realization of this societally motivated aim as a gradual and sequential evolution from ideas, plans, and hypotheses into an artefactually created material outcome, the transgenic plant. This process was constrained by multiple drawbacks, such as resistance (Pickering 1995), as well as alterations in collaboration networks, which required revision of plans and accommodation of the research object and methods (Suchman 1987). To supply an explanation for the change of the systems I shall refer to the compelling analysis on the Drosophila genetics supplied by Robert Kohler. He described the invention of a new experimental system (Kohler tivated potato. The words “strategy” or “manner of thought” were used to describe one way or the other of developing virus-resistant plants. In the research proposals, the experimental systems were described and summarised as a series of actions, tools, and methods used. 4. In the wild-potato system, the increase in the virus resistance was expected to result from the transfer of the natural resistance genes to the cultivated potato. In the viral-gene system, introduction of a viral gene into a plant was believed to result in a similar effect.

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Table 1. The wild-potato system and the viral-gene system of the research programme. Phase 1: the wild-potato system

Phase 2: the viral-gene system

1. Motive of the group’s research work

—to create virus resistant potato (application object) and to understand the resistance mechanism (epistemic object)

—to create virus resistant potato (application object) and to understand the resistance mechanism (epistemic object)

2. Working hypothesis of the virus-resistance mechanism to be constructed and used

—introducing natural virusresistance genes into the cultivated potato will cause the virus resistance effect

—introducing a viral gene into the cultivated potato will cause the virus resistance effect

3. Basic materials, tools, devices and methods

—large DNA fragments consisting of multiple resistance genes of the wild potato —cell fusion by using a speciªc device —genetic mapping and fragmenting of DNA with markers and pulsed-ªeld gel electrophoresis —electric or biological transfer of the DNA fragments

—a single viral gene —gene isolation by using PCR and standardised tool kits —gene transfer by using a biological vector

1994, pp. 257–258): “[E]xperimenters change course when doable practices make this possible with minimal sacriªce of production. New practices evolve gradually as elements of established practices are modiªed and rearranged, in a way that is highly contingent on the particularities of local working groups.” This kind of gradual evolution of the new experimental system took place also within the Pehu group. As will be shown, the following concepts were crucial for this process: network collaboration, ad hoc improvization, resistance, opportunism, shifts between research tools and objects, and appropriation of ideas and tools from outsiders. Since these instances were neither fully controlled nor anticipated by the group, the transformation of systems involved also a strong element of contingency. These sources of dynamics were also interconnected. The change of systems, as such, could not be attributed to any individual cause; none of them alone was potent enough to effect the change. However, when they all occurred together within a relatively limited period of time, their combined force induced transformation.

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3. Dynamics of Objects in Wild-Potato Systems: Studying Virus Resistance Phenomenon and Creating Virus-Resistant Cultivated Potato

Collaboration Networks in Studying and Using Wild Potato’s Inherent Virus Resistance

In alignment with the dual focus of the research programme, the group attempted both to reveal the virus-resistance mechanism in the wild potato (Solanum brevidens) and to construct the cultivated potato with an increased virus-resistance trait. At the level of the group’s working organisation, these concerns were organised into two distinct and parallel research projects.5 Although thematically interlinked, interconnection between the projects remained slender at the level of the actual working practice. The projects were: (1) description and analysis of the natural virus-resistance trait in the wild potato by Mr. Jari Valkonen (1992) and (2) localization of the resistance genes in the wild potato and their transfer to the cultivated potato by Mr. Yong-Sheng Xu (1993). These projects constituted two distinct wild-potato systems with varying emphases on the epistemic and practical aspirations. The ªrst project, which was accomplished in collaboration with scientists working in Peru, Chile, and Argentina, drew special attention to the construction of new knowledge on the wild potato’s virus-resistance trait. It was set to describe and analyze the whole diversity of the plant’s resistance to those viruses that effected major damage in potato production. Additionally, the project aimed at studying the mechanism of virus resistance in the wild potato at the cellular level and the plant’s tolerance to virus-transmitting aphids. Despite the epistemic emphasis, the project was motivated by the prospective use-value of the research results: A major part of this project is, therefore, to investigate the mechanism(s) of virus resistance in S. brevidens [the wild potato], both because of its intrinsic scientiªc interest and because a [...] source of broad-spectrum virus resistance would be of practical value to breeding and/or genetic engineering of potatoes for resistance (Research Proposal 1989). The second project addressed the dual research object more vividly. It attempted to transfer the virus-resistance genes of the wild potato to the cultivated potato to enhance its tolerance to viruses in the ªeld. However, 5. Also a third project was started. In this project, Ms. Tuula Pehu pursued to uncover whether a speciªc gene of a potato virus was responsible for the virus’s movement in plants. This study can be regarded as a predecessor of the forthcoming viral-gene system.

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realization of this applied objective depended on the construction of an epistemic object, since the virus resistance genes of the wild species had to be localized and isolated before they could be transferred. Just as the ªrst project, this research also depended essentially on cooperation with other scientists. Especially the contribution by Dr. Michael Jones’s group working at the AFRC Rothamsted Experimental Station, England, was of crucial importance. It was this collaborative context where the group developed its research ideas, and the conceptions of how these should be approached experimentally, as well as its tools and plant materials.6 Such a strong dependence on the collaboration networks was derived from the group’s being a newborn community of researchers and among the very ªrst at the Faculty of Agriculture and Forestry to make use of modern plant biotechnology. In the early 1990s, neither workable laboratories nor adequate know-how were ready and available. Hence, a working group to equip a molecular-biology laboratory was organised at the Faculty. However, many research materials, tools, and instruments as well as experimental skills were not obtainable right away (Pehu T. Interview 1997; Pehu E. Interview 1998). Due to this, networking became a key mechanism for the group to secure the means indispensable for the pursuit of its research object. Mutual dependence between the object of activity and the social network is suggestive of Michel Callon’s (1980) early analysis of a fuel-cell research programme. In his case, building up a research programme was a process of setting hypotheses and research questions, and, concurrently, mobilizing appropriate social actors with the required knowledge and instruments. In my case example, the different versions of the wild-potato system can be understood as concurrent formations of the object of activity and the networks of actors contributing to its transformation and realization.7 The outside actors that participated in the experiments on the basis of their particular knowledge, methods, and materials contributed signiªcantly to the deªnition of the Pehu group’s research object. The wild-potato systems and the collaboration networks were reciprocally constitutive. 6. In the late 1980s, the group leader worked at the Rothamsted Station accompanied by three of her students. The idea of using the wild potato as a source of virus resistance emerged from this research. 7. This might be called co-construction of the research object and collaboration networks, cf. Law and Callon (1992), Pickering (1995), Fujimura (1996) and Miettinen (1998).

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Mr. Xu’s project, which aimed at revealing the virus-resistance genes and creating the virus-resistant cultivated potato, was a laborious task consisting of multiple phases. When starting the work, the researchers did not know which genes in the wild potato caused the resistance; these had to be localized. Thus, the initial stages of the object construction involved producing new knowledge. This was accomplished by, ªrst, creating suitable plant material by hybridising the virus-resistant wild potato and the virus-susceptible cultivated potato, and second, by using these potato hybrids as tools for localizing the DNA fragments that contained the resistance genes. In this research, new techniques such as pulsed-ªeld gel electrophoresis, species-speciªc probes and genetic markers were utilized. The application object was addressed, ªnally, in the third phase of the experimentation. It consisted of the realization of the virus-resistant potato by transferring the localized and isolated DNA fragments to the cultivated potato. Understood in this way, the experimental system is exempliªed as a series of phases in the object construction process. In each phase, plant materials and other research substances are subjected to complex manipulations with elaborate tools, instruments, and methods. The relationship between objects and tools is dynamic: objects are constructed by using tools, but when the limits of the tools are faced they may also become objects. And the other way around: once an object is constructed and stabilised it may become a tool used in further research. The same entity can, thus, be either an object or a tool (Latour and Woolgar 1979, p. 110) depending on the phase of the activity; constant shifts between them are constitutive for the development of the experimental systems, as pointed out by Kohler (1994, pp. 147 and 156) and Rheinberger (1992a; 1995, p. 111), and elaborated by the activity theory (Engeström 1990, pp. 171–195; Miettinen 1998, p. 431). In this case, the plant material created in the ªrst phase was used as a tool in localizing the resistance genes in the second phase. In the third phase, the knowledge on the positions of resistance genes in the plant genome was used as a resource to create the virus-resistant potato. Due to the complexity of the ªrst version of the wild-potato system, its realization involved mobilization of the relevant partners with speciªc cultural resources. Because the Pehu group had its roots, both material and conceptual, in a group led by Dr. Michael Jones of Rothamsted Experimental Station, that group was a natural associate. Its contribution was most important in the ªrst phase of the experimentation. Although the

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Pehu group had already obtained some hybrid plants from the Rothamsted Station, even more raw material was needed. This was a practical imperative for both the localization of the resistance genes and for the creation of the virus-resistant potato. The Jones group, having the cell fusion device and having made potato hybrids before, was set to produce this material. The second phase of the experimentation, the localization of the resistance genes was accomplished by the Pehu group itself. In this work, the electrophoresis device of the neighbouring department was applied in addition to the speciªc tools (DNA probes and genetic markers) developed or acquired by the group. And the third phase, the transfer of the resistance genes, was performed again by the Jones group by using either an electric technique (electroporation) or a biological agent (Research Proposal 1989; Pehu E. to the Author, November 27, 1999). However, the joint work with the wild-potato system had hardly started when a major setback befell the Pehu group quite unexpectedly. The Jones group was discontinued, and the initial network of collaboration broke down. The disintegration of the group was an outcome of the reorganization of the activities of the Rothamsted Station at the turn of the 1990s: the group was disbanded, and its leader, Dr. Jones, moved to Murdoch University, Australia (Valkonen Interview 1997; Pehu E. Interview 1999). In consequence, the research using this wild-potato system could not even be properly started before its social and material basis collapsed. The Pehu group lost access to the large amounts of potato hybrids that were crucial to the work. It also lost access to the fusion machine and the related know-how. The group was poised in a dilemma: ambition to create the virus-resistant potato frustrated by the lack of the indispensable tools, instruments, and methods. What was the group’s reaction? Initially, they made an attempt to re-establish collaboration networks as well as experimental set-ups in an ad hoc manner (Suchman 1987, pp. ix and 51; Garªnkel 1989, pp. 20–22). This resulted in the emergence of two new research partnerships. In both cases, the object of activity changed as a result of retooling by the partners (Kohler 1994, pp. 175 and 206). New Partnership with the Lapitan Group: Research Techniques Became Objects of Study

In the effort to re-establish the network between 1991–92, Dr. Pehu contacted the following researchers: (1) Prof. Kristina Glimelius at Swedish University of Agricultural Sciences, (2) Prof. Nora Lapitan at Colorado State University, and (3) Prof. Elizabeth Earle at Cornell University (Lapitan to Pehu E., January 29, 1991; Glimelius to Pehu E., January 31, 1992; Research Proposal 1992; Pehu E. Interview 1997; 1999). An important reason for choosing these partners, besides the already existing

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personal contacts, was the access through them to complementary research methods. As noted by Dr. Pehu, Prof. Earle’s group was pursuing partial genome transfer just like the Pehu group, Prof. Lapitan’s group had specialized itself with the methods of localizing speciªc DNA sequences in plants, and Prof. Glimelius’s group was doing with another plant what the Pehu group intended to do with the potato (Pehu E. Interview 1999). After some correspondence, Dr. Pehu came to an agreement about joint research with professors Lapitan and Glimelius. In comparison with the original experimentation designed with the Jones group, the new wild-potato system was transformed and reduced. It was scaled down by dropping the ªrst phase of the original system. No further fusions were made, and the groups decided to proceed with those potato hybrids that had already been acquired from Rothamsted Station. The shared experimental system consisted of two major parts: First, large DNA fragments were obtained from these potato hybrids. And second, these isolated fragments were transferred to the cultivated potato by utilising yeast artiªcial chromosomes as vectors. At the ªrst stage, the DNA probes developed by the Pehu group were combined with the in situ hybridization method developed by the Lapitan group. The contribution of the Glimelius group (based on a speciªc device, a ºow sorter) was considered an alternative to the technique of the Lapitan group. Late in 1992, the experiments were started in two laboratories. Scaling down the original experimentation prevented, however, the establishment of an effective breeding programme. Because no further fusions between the wild and cultivated potatoes were made, the plant material was too limited for creating the virus-resistant potato. Nevertheless, it was quite enough to test the research technology for the future practical purposes. Mr. Xu did this work at the University of Helsinki. After constructing ªve molecular maps of the hybrid potatoes, he and Dr. Pehu gave the following verdict on the practical applicability of the technology in potato breeding: [. . .] limited chromosome elimination has been found and the irradiation resulted in extensive chromosome rearrangements and chromosome breaks. These are serious drawbacks in application of this technology for practical breeding purposes (Xu and Pehu 1993). Concurrently, Dr. Pehu started joint research at the Lapitan laboratory. There she began testing the applicability of species-speciªc probes as combined with the in situ hybridisation method in localizing speciªc DNA sequences in the wild potato. However, the concrete attempts of these experiments revealed that the work was not so feasible as expected. As noted by her, the research was so “massive,” “extremely laborious,” and “boring”

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that it was left unªnished although the scientiªc answers regarding the genetic control of the resistance trait would have been “highly interesting” (Pehu E. Interview 1998). The technologies were not advanced enough for studying that question effectively (Valkonen Interview 1997). On the basis of the analysis thus far, the following conclusions can be drawn. The ad hoc improvisation initiated by the group leader in the form of re-networking and the tools and methods so acquired proved insufªcient. First, the experimental system did not allow the group to produce new hybrid potatoes, although these would have been indispensable for the construction of the virus-resistant potato (application object). Second, resistance (Pickering 1995; Rheinberger 1996, p. 415) emerged in the work with these potato hybrids the group already had. Owing to the relevance of the technology from the practical point of view, the research became questioned. And third, the localization of the resistance genes in these hybrids (epistemic object) proved impossible as a result of undeveloped research techniques. Collaboration Between the Pehu Group and Agricultural Research Centre: Construction of Objects Fails but New Beneªts Emerge

In 1993, yet another concurrent experimental system aiming at bringing about the research object was initiated. This time, a small joint project by the Pehu group and researcher Veli-Matti Rokka of the Agricultural Research Centre of Finland was used as a springboard. On that basis, an extensive new project was undertaken. The project combined the work of revealing the resistance mechanism in the wild potato with the production of the cultivated virus-resistant potato. By interlinking these concerns, the project formed a research package in which both parts of the research object, the epistemic as well as the applied, were pursued simultaneously. First, the work by Mr. Rokka at the Research Centre aimed at transferring the virus resistance genes of the wild potato into the cultivated potato. Having access to the cell fusion device, he extended the plant material basis of the experimental system by producing a number of new hybrids between the wild and cultivated potatoes.8 Second, Jari Valkonen of the Pehu group continued his research on the virus-resistance mechanism in the wild potato. By 1992, he had ªnalized his dissertation on the characterization of the natural resistance trait and, now, he pursued a more thorough understanding of the resistance mechanism itself. Since 1993, these studies expanded into an independent research programme address8. However, some fusions were also made for the sole purpose of the fundamental research on the resistance mechanism and genetics (Valkonen and Rokka 1998; Rokka Interview 1998; Rokka and Pietilä Interview 1998).

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ing the question at the cell and molecular levels combined with the attempt to reveal the genetic regulation of the resistance phenomenon.9 The experimental system resembled the original experimentation designed with the Jones group in the respect that new plant material was being produced. The number of chromosomes in the hybrids, however, was reduced for the practical purposes, in the second phase. And, in the third phase, the potato hybrids with the reduced chromosome number were, once again, hybridized with the cultivated potato also having a reduced chromosome number (Rokka 1998).10 The division of labour between the participants was clear. First, Prof. Pehu, who was in charge of the project, encouraged Mr. Rokka by giving him ideas and helping as requested. Dr. Valkonen studied the virus resistance of the hybrid potatoes and provided other researchers fundamental virology knowledge. The concrete manipulation of the plants was done by Mr. Rokka and his technicians by using the fusion device and other tools provided by the Research Centre. And ªnally, breeder Pietilä kept the research under observation for the possible use of its results in breeding work. The research applying this experimental set-up for the creation of the dual research object was done between 1994–96. Two separate attempts to bring about the virus-resistance effect in cultivated potato were accomplished. Despite some limited success, the results, however, indicated severe difªculties in making use of the wild-potato genes. The object hypothesis according to which introduction of the natural resistance genes into the cultivated potato would cause virus resistance was “resisted” by the experiments. As concluded by Dr. Valkonen (Research Report 1997): The data relevant to this project can be summarized by stating that virus resistance could not be transferred from S. brevidens to cultivated (S. tuberosum) gene pool. Resistance was strong in many somatic hybrids, but when these hybrids were “crossed” [. . .] with dihaploid potato lines, only weak or no resistance was observed in the resulting hybrids. Despite this difªculty, the research was advantageous both in terms of fundamental science and practical application. Instead of the virusresistant potato, a large amount of useful plant material was created and 9. A part of these studies was done in collaboration with Mr. Rokka and with scientists working at the Cornell University. For these studies, see Research Report (1997); Valkonen Interview (1997) and Valkonen to the Author (April 7, 2000). 10. The model for the experimental system is presented in Rokka (1998, p. 41). The reasons for such a unique and complex set-up had to do with the practical aims of the researchers: for instance, ordinary sexual crossing could not be used because of the low fertility of the “ªrst-generation hybrids” and the risk of losing agriculturally valuable traits.

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new breeding methods were developed (Rokka 1998; Rokka Interview 1998; Rokka and Pietilä Interview 1998). Later, these were transferred from the Rokka group into the laboratory of Boreal Plant Breeding, a subdivision of the Research Centre, where they became utilised as a part of the breeding practice. Second, the research supported the theoretical assumptions postulated by the Pehu group. It provided further evidence for the hypothesis according to which the resistance to viruses in the wild potato was related to the restricted virus movement in the host plant. And third, as the agriculturally important resistance trait became described in greater detail, the wild potato became a suitable model plant11 for further studies on the virus movement and for cell fusions at the diploid level of potato. 4. Gradual Process of Inventing Viral-Gene System and Transgenic Virus-Resistant Cultivated Potato

At the same time as the Pehu group was engaged in making use of the various versions of the wild-potato system, a new viral-gene system was gradually emerging (Research Proposal 1993; Pehu E. Interview 1998). Although this system can be considered a logical application of the pathogen-derived resistance concept of the time, it was an entirely new approach within the Pehu group. It aligned the group’s work with the fast-pacing international research front in plant genetic engineering, and, as such, it may not be entirely wrong to regard it as an example of “the bandwagon effect” as analyzed by Joan Fujimura (1988).12 Given the new experimental and theoretical context of pathogen-derived resistance, the change of experimental approach also induced alteration of the working hypothesis and the epistemic object. Within the viral-gene system, the hypothesis comprised the assumption according to which introduction of a viral gene would result in resistance effect in the transgenic plant. Comparatively, the epistemic object was the mechanism of such genetically engineered resistance phenomenon. The change of experimental systems did not take place all at once. Rather, it was incremental, a process whereby results accumulated over time seemingly effected a sudden emergence of the new system in 1993. 11. For model organisms in biology, see Rheinberger (1992b, pp. 391–392). Kohler (1994) speaks about model organisms, such as Drosophila, as standard laboratory instruments. 12. According to Fujimura (1996, p. 2), the scientiªc bandwagon exists when “large numbers of people, laboratories, organizations, and resources become committed to one approach to a problem.” In cancer research, the bandwagon effect was facilitated by the standardized package of oncogene theory and recombinant DNA technology. Kohler (1994, p. 254) also uses the notion of a bandwagon.

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However, the history of the system can be traced back to the very beginning of the Pehu group’s research programme on the potato virus since 1990 and to the studies on the wild potato’s resistance mechanism since 1992. Within a couple of years, this network of independent, but thematically interlinked projects proved constitutive for the renewal of the group’s experimental approach. It created a basis from which a variety of new tools (the viral gene) and methods (genetic transformation) arose. Later, these exceeded the scope of their original use context and became appropriated as basic constituents of the new, emerging experimental system.13 The viral-gene system came into being when these outcomes were combined with the new results acquired from the group’s international partner. The motive for the Pehu group to develop and adopt the new experimental system was, indeed, their aspiration to create the virus-resistant potato. Given the difªculties experienced with the wild-potato system, experimenting with the viral-gene system seems only rational. As noted earlier by Andrew Pickering (1995, p. 59) and Robert Kohler (1994, p. 248), experimental scientists often work quite opportunistically. They follow problems and use experimental systems that are most productive and abandon those that are not. For the Pehu group, the viral-gene system proved faster and simpler than the wild-potato system, enabling the researchers to overcome the limitations of the earlier system, and realize their applied aspiration. The Pehu Group Adopts and Constructs New Tools, Methods and Know-How That Form the Basis for the Viral-Gene System

Studies concerned with the virus-resistance mechanism were based on an assumption that a speciªc gene (P1) in a potato virus might be the movement gene of that virus. To determine whether this supposition was right or wrong, Ms. Tuula Pehu, sister of Prof. Pehu and a researcher afªliated with the group, started isolating and cloning the gene. In 1991, the work ran, however, into experimental difªculties, and started to fall behind in the schedule. Despite her numerous attempts, Ms. Pehu did not succeed in isolating the viral particles that included the gene. In this situation, the group discussed the problem but could not solve it. At that time, Ms. Pehu attended a conference in the United States where she conversed with Michael Jones, whom, on the basis of their previous collaboration, she 13. Many studies note the constitutive role of new tools and methods, and how these former objects become materially mediating artefacts of the work subsequently. See Kohler (1994, p. 173), Fujimura (1988; 1996), and Miettinen (1998). Rheinberger (1993, p. 470) adds an important point into these accounts: “instruments themselves are not the moving forces of scientiªc going-on: it is their embedment into experimental system that counts.”

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asked for a piece of advice. Having recently cloned another gene, Jones suggested a new PCR-based method that was becoming a standard approach in gene cloning:14 [ . . . ] ªrst, I tried to clone that gene by using the cloning technique traditional at the time. And it didn’t work [ . . . then] I changed over, as suggested by Jones, to PCR, which meant that I could manage . . . the work that had taken weeks earlier, in one week (Pehu T. Interview 1998). In addition to the work of determining the function of gene P1, the natural resistance mechanism was studied simultaneously. In these studies, Dr. Valkonen endeavoured to reveal whether a restricted cell-to-cell spread of viruses constituted the basis of resistance in the wild potato. To accomplish these experiments, a genetic-transformation method was needed and developed. For the work, an undergraduate student, Kimmo Koivu was recruited. In fact, Mr. Koivu was not the ªrst researcher to develop a genetic transformation method within the group. Before him, another student had already worked on such a method (Suomaa 1994). However, the method had to be optimized for the wild potato. This proved exceedingly difªcult. Moreover, neither the know-how nor the tools used by the previous student passed over to Mr. Koivu (Koivu Interview 1997). Consequently, he had to start from scratch, lacking many indispensable tools as well as the necessary knowledge. On the basis of his previous contact, Mr. Koivu was able to acquire some of these from the Institute of Biotechnology, University of Helsinki.15 Despite this help, he often had to proceed with the research tasks all alone using a simple method of trial and error. By making an extensive number of experiments, he ªnally succeeded in producing the wild potato altered with the gene of the tobacco virus (Koivu 1994; Koivu et al. 1995; Koivu Interview 1997). Unpublished Results of the Zaitlin Group Prompt Creation of Transgenic Virus-Resistant Potato by Using Emergent Viral-Gene System

A decisive input to the work by the Pehu group that ªnally induced the researchers to experiment with the viral-gene system came through the in14. Dr. Jones also suggested the use of a new version of Invitrogen’s TA Cloning Kit. With the help of that tool Ms. Pehu was able to work with her PCR products more effectively. For PCR and related molecular biological techniques, see Jordan and Lynch (1992; 1998); Lynch and Jordan (1993; 1995; 2000) and Rabinow (1996). 15. The tools provided by Dr. Teemu Teeri’s group included a transformation vector, a helper plasmid, Agrobacteria, and know-how of re-growing genetically altered plants.

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formal networks. As noted in many studies, such connections and communications are of crucial importance in fostering innovation and regulating the ºow of information and material resources below the level of institutionalised collaboration (Kohler 1994, chap. 5; Rheinberger 1997, p. 138; Atkinson et al. 1998).16 For the researchers of this particular group, such networks served as reserves for new tools and ideas. In a personal communication between the group leader and her acquaintance, the latter informed the former about unpublished research results obtained by a Cornell-based Zaitlin group. These inspired the leader to employ the already existing tools and methods locally in an entirely new way, that is, to genetically transform the cultivated potato with the viral gene. Quite soon, this new experimental system proved easier and more productive in bringing about the group’s applied object. The use of viral genes as mediators for resistance became known as the pathogen-derived resistance concept (PDR). Originally, the invention was made by Roger Beachy’s group at the Washington University in Saint Louis. In the early 1980s, that group performed a series of experiments where plants were transformed with a gene derived from a tobacco virus. In the resulting transgenic plants the disease development was delayed. After success with four different viruses, the results were considered generalizable, and it was thought that only one mechanism of the PDR existed (Beachy 1999; Beachy Interview 1999). This standpoint proved wrong, however, in the early 1990s as more experiments were performed. The Beachy group had introduced into plants so-called viral coat-protein genes. In the early 1990s, other groups, such as Milton Zaitlin’s at the Cornell University, William Dougherty’s at the Oregon State University and Eija Pehu’s at the University of Helsinki, produced a number of transgenic plants that exempliªed new forms of PDR. In these experiments, plants were altered with new kinds of viral genes. As these genetically altered plants were studied, it appeared that they were resistant to viruses but that the underlying biological mechanisms were different from the original form of the PDR. The practical experiments, thus, induced signiªcant conceptual change and diversiªcation of the original under16. In my case example, the informal contacts were mostly managed by the group leader, who appeared to be the most inºuential actor in mapping out the new lines of research. She also actively linked the work of the group to issues external to the laboratory. In regard to this, Knorr-Cetina (1999, pp. 221–224) spoke about group leaders being oriented towards society, or more precisely, “toward those elements in a social ªeld that are relevant to laboratories.” In terms of Fujimura (1987), this kind of orienting could be called articulation work, meaning the incorporation of interests of researchers with those of their audiences.

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standing of the studied phenomenon, as excellently discussed by Robert Kohler (1994, pp. 54–56). The ªrst instance of these new variants was created by the Zaitlin group, a large body of researchers enjoying a central position in the area of plant genetic engineering and virology. Working with theoretical questions, the group was the ªrst to invent the connection and make use of the fact that also other viral genes than those used by the Beachy group mediated resistance.17 Before these results were published, Prof. Pehu heard about them from her colleague in the United States. This information was decisive. The use of a new kind of gene was something truly different: this gene (called the replicase) was quite similar to P1, and moreover, it was derived from the very same potato virus as P1 was. Says Eija Pehu: Interviewer: What has been the signiªcance of the idea of the pathogen-derived resistance to the development of your research programme? Eija Pehu: Decisive; the observation that almost any [gene] sequence of the potyvirus can mediate resistance. At the time, it had already been demonstrated for the coat-protein, and there was this rumour about the replicase, that it can be used [to mediate resistance]. And we got the opportunity of introducing P1 (Pehu E. Interview 1999). In a working discussion with her research group in 1993, Prof. Pehu introduced the idea of transferring gene P1 to the potato. The group decided to take advantage of this chance to create the virus-resistant potato. As noted by one of the researchers, the idea appeared suddenly: “It popped out, it was simply plucked, grabbed hold of, as it were, into our design after a while” (Pehu T. Interview 1997). Recalls Prof. Pehu: I remember one working discussion and a meeting where I just said that let’s transfer that [gene] to the plant, what if it would disrupt the infection and we would get resistance, just as using the coat protein. [ . . . ] And then, the ªrst results by Milton Zaitlin came out, and we heard from Cornell that, hey, the replicase does it too. It was customary to think [about the coat protein] that it is the very protein which [ . . . effects the resistance]. But replicase was 17. This invention was serendipitous. The original aim of the Zaitlin group was, instead of engineering virus resistance, to ascertain the function of a tobacco mosaic virus gene. Later, the group also experimented successfully with the replicase derived from the genome of the potato virus. It was this latter result which prompted the use of gene P1 as a resistance factor by the Pehu group (Zaitlin Interview 2000; Zaitlin to the Author, August 1, 2000).

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something different, really, [ . . . ] And our P1 was similar, exactly (Pehu E. Interview 1998). The idea was not revolutionary, as such, neither was it clear that it might work. But to experiment with yet another kind of gene was a logical step forward from the Zaitlin group’s result. The group attempted to put it into practice immediately by using its new transformation method and the isolated gene P1. A project was established and a researcher, Ms. Tuula Mäki-Valkama, recruited to continue the group’s previous work and to construct a future prospect of how the gene and the transformation method could be utilised as tools in the emergent viral-gene system. The working hypothesis proposed that transferring gene P1 into an already useful potato cultivar should result in a practically sufªcient degree of resistance (Research Proposal 1997). The researcher received the isolated gene from her colleague and was taught and helped to introduce it into the potato (Pehu T. Interview 1997; Mäki-Valkama Interview 1997; 1999). Basically, the viral-gene system, which combined her project with that of Ms. Pehu, comprised the following main phases: (1) isolation of gene P1 from the potato virus and (2) transfer of that gene into the cultivated potato.18 The experiments were successful, and, in consequence, altered the group’s research practices in a broad sense. Besides the already existing wild-potato system, the viral-gene system remained housed at the group’s laboratory. For several years to come, the group pursued these two experimental systems simultaneously. On the one hand, the researchers went on studying the natural virus-resistance mechanism in the wild potato and attempted to make use of it in the potato-breeding practice. On the other, they started to work with transgenic virus resistance more systematically. The genetically altered plants possessed a scientiªcally novel resistance phenomenon.19 Thus, a dual research object arose within the viral-gene system just as was the case within the wild-potato system. First, the researchers started to apply the genetic-transformation methods to create virus-resistant cultivated potatoes, to study whether the resistance endured in the ªeld, and whether the transgenic plants produced tubers (application objects) and, second, they strove to understand the new 18. In fact, this account of the experimentation is presented as being more determined than it actually came out. For example, in the beginning of the research the group believed that the P1 gene should be inactivated before it could be used to induce resistance. 19. This new genetically engineered resistance phenomenon was named gene silencing. In 1993, it was an evolving concept within the global research community committed to the study of pathogen-derived resistance. Subsequently, Ms. Mäki-Valkama worked to determine the exact mechanism of gene silencing in the potatoes transformed with the P1 gene.

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epistemic object, that is, the underlying biology of gene P1 mediated resistance. The group also started a commercial exploitation of the results. A local university licensing ofªce contacted the researchers with the aim of patenting the invention. Subsequently, the patented living organism and the methods of producing it became mediators between the research accomplished at the university and the international plant-breeding business. At this stage, the commercial objectives and epistemic aims started to differentiate from one another (Pehu E. Interview 1999). In the years that followed, both of these lines of work were accomplished in cooperation with different partners; the virus resistance mechanism studies jointly with the Zaitlin group, and the application work with a Danish plant-breeding ªrm. 5. Conclusions

Epistemic objects are important loci of analysis in the study of scientiªc practices. To address them, Hans-Jörg Rheinberger has made a major contribution to the conceptual apparatus. Focus on epistemic things alone, however, does not do justice to some ªelds of research, but an expanded understanding of the objectives of the research work is required. My aim was to investigate one of those ªelds, namely, plant biotechnology. By submerging myself in the work of a local research group in that area, I sought to exemplify the necessity of acknowledging the built-in utility value of scientiªc research, besides its epistemic aspects. The main contribution for social studies of scientiªc practice is to suggest an expanded deªnition of the experimental system and to illustrate how it might be applied. For this, the concept of dual object was introduced. It was incorporated into the analysis of the experimental systems to make them accountable for both basic scientiªc concerns and societally signiªcant applications. In my usage, the application object pointed to the virus-resistant cultivated potato under construction, and the epistemic object to the knowledge on the virus-resistance mechanism. During the course of the research, these objects rested on each other in many ways. For example, the failure to bring about the virus-resistant potato implied the impossibility of studying the genetics of the wild potato’s resistance, and the construction of the transgenic virus-resistant potato brought about a novel resistance phenomenon for later scientiªc investigation. The two phases of the research programme were conceptualized as different experimental systems, the wild-potato system and the viral-gene system. Both of them were based on speciªc hypotheses and comprised multiple phases in which complex manipulations of research materials by a whole variety of tools and instruments were carried out. The transition

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from the wild-potato system to the viral-gene system was understood in terms of a gradual evolution characterised by many features, such as network collaboration, ad hoc improvization, resistance, opportunism, as well as informal interaction. Using these concepts allowed me to give an account of experimental systems as exceeding the boundaries of single laboratories while being fundamentally local accomplishments, at the same time. After several attempts, the studied group was able to bring about its objective, the potato cultivar, which had an increased ability to resist viral infections in the ªeld. The type of resistance now manufactured had not existed, as such, in nature, but was a result of artefactual human intervention (Hacking 1983). After its production, the epistemic and the applied dimensions of the research became more clearly separated. One line of work aimed at revealing the biological mechanism behind the resistance effect. Another line, then, attempted to further develop the created resistance effect from the practical-commercial point of view. In these studies performed in collaboration with a plant breeding enterprise, the constructed model system was extended from one strain of the virus to multiple strains. Once this work was accomplished, the outcome became commercially even more attractive and exploitable than the original invention. A signiªcant feature of the case was that the decisive changes in the group’s practice took place in the technical and epistemological realms only. The context of application had no other direct inºuence to the research than what was built-in to its object of work from the very beginning, that is, the aim of improving virus-disease management by means of creating a virus-resistant potato. This inbuilt practical objective was, however, vital: it made the group experiment with the emergent viral-gene system, a work which resulted in both a useful transgenic potato and new scientiªc knowledge. The concept of experimental system proved useful in analyzing the early phases of the research programme. However, as the work started to expand from the research laboratory to the domain of the plant-breeding practice, the need for further theoretical work became evident. The system-of-production concept introduced by Robert Kohler might prove a useful starting point for such theorizing. Kohler wanted to underline the fundamental similarities between science and other social activities by which he means that both are “collective, marketplace activities, driven and constrained by the production process and by the activities of consumer or user constituencies” (Kohler 1991, p. 88). However, Kohler himself uses the market terms in a metaphorical sense only, and does not address the compelling and pregnant issues of science-society interaction, in particular.

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To do this, it might be helpful to look for ideas from the recent dialogue between cultural-historical activity theory and actor-network theory (Latour 1996a; 1996b; Engeström 1996; Miettinen 1998; 1999; Lehenkari 2000). In this context, it has been proposed that innovation process and interaction between scientists and users could be studied as networks of local activity systems, such as research groups and companies. The advantage would be in making the co-operation comprehensible in terms of the joint object construction by distinct actors. In such networks, the participants mobilize their historically-formed cultural resources for the construction of the object. Their involvement arises from the problems experienced in their own work activity, and from their aspiration to use their expertise in new ways. Such a framework might render crucial practical aspects, such as mutual learning and conºicts among participants, analyzable as integral parts in the transformation of an experimental system into a commercial production system. References

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