612146

research-article2015

SSS0010.1177/0306312715612146Social Studies of ScienceFukushima

ArticleConstructing failure in big
biology: The socio-technicalanatomy of Japan’s Protein
3000 Project

Social Studies of Science
2016, Vol. 46(1) 7­–33© The Author(s) 2015
Reprints and permissions:sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0306312715612146
sss.sagepub.com

Masato Fukushima

The Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan

Abstract
This study focuses on the 5-year Protein 3000 Project launched in 2002, the largest biologicalproject in Japan. The project aimed to overcome Japan’s alleged failure to contribute fully to
the Human Genome Project, by determining 3000 protein structures, 30 percent of the global
target. Despite its achievement of this goal, the project was fiercely criticized in various sectors ofsociety and was often branded an awkward failure. This article tries to solve the mystery of why
such failure discourse was prevalent. Three explanatory factors are offered: first, because somegoals were excluded during project development, there was a dynamic of failed expectations;second, structural genomics, while promoting collaboration with the international community,
became an ‘anti-boundary object’, only the absence of which bound heterogeneous domestic
actors; third, there developed an urgent sense of international competition in order to obtainpatents on such structural information.

Keywords
anti-boundary object, big science, expectations, Japan, structural biology, structural genomics

Introduction
In 2005, the journal Nature published an unusual review of a book that had beenreleased only in Japanese (Ito, 2005). Written by Nobuhito Kishi, a journalist specializing in intellectual property, Genomu Haiboku: Chizai Rikkoku Nihon ga Abunai or
Corresponding author:
Masato Fukushima, The Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba,
Meguro-ku, Tokyo 153-8902, Japan.
Email: maxiomjp@yahoo.co.jp

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Social Studies of Science 46(1)Defeat in the Genome: Japan’s National Policy for Intellectual Property in Danger(Kishi, 2004) conveyed a sense of urgency concerning Japan’s gloomy economic
prospects, which it argued were caused by continuous ‘defeats’ in an international war
for intellectual properties.
Perhaps reminiscent of John Osborne’s stage play of that name, Kishi describes his‘look back in anger’ about what happened in the Japanese genomic research policy. The
opening of his book eloquently reveals his undisguised indignation:
The traumatic thought weighing on the person’s mind straightforwardly narrates the tragedy ofJapan’s ‘defeat in the genome’. His DNA-decoding scheme should have been five years ahead ofthat of the US … More than twenty years before, at the end of 1970s, he was nursing the originalidea of high-speed machine for decoding the genetic information of DNA. (Kishi, 2004: 3–4)

The person referred to here is Akiyoshi Wada, a leading biophysicist whose pioneering
steps in proposing an automated sequencer, based upon the Maxam–Gilbert method, arethe topic of the first half of Kishi’s book (cf. Wada, 2005: 136–138; Wada et al., 1983).
Wada launched a project for its development in 1981, which brought together both scientists and leading industries. Later, Charles Delisi, the director of the Department of Energy’s
Health and Environment Program, was alarmed to find that Japan was 5 years ahead of theUnited States on the DNA sequencing project (Cook-Deegan, 1994: 215–216, ch. 5).
Kishi eloquently narrates how such Japanese inventions as four-color fluorescentlabeling in 1982 and the Capillary Array DNA Sequencer from Hitachi in 1993 (cf.
Anonymous, 2001) were ruined by a series of blunders rising out of conflicts between
competing ministries, as well as by the shortsightedness of scientists about the possible
future of such technologies.1 Thus, the US Congress, Office of Technology Assessment’s(1988) comprehensive report on the prospect of the Human Genome Project (HGP) dispassionately described the weaknesses of Japan’s move, and by the end of the HGP,Japan had contributed only 6 percent of the decoding, in contrast with 59 percent for theUnited States and 31 percent for the United Kingdom.
In the latter part of the book, the tone changes from indignation to hopefulness, and thisshift is because of the topic of this article: the Protein 3000 Project, launched by theJapanese government in 2002. Apparently having learned bitter lessons from too-small
support and too-late timing, the merged ministry of the Science and Technology Agency(STA) and Ministry of Education (hence Ministry of Education, Culture, Sports, Scienceand Technology, or MEXT) promoted the project, pouring an unprecedented amount of¥53.5 billion (US$618 million) into all Japanese teams of structural biologists for a projected analysis of 30 percent – not 6 percent – of the 10,000 protein structures agreed uponby the international community of structural genomics.
In 2007, MEXT’s Life Science Committee created a project evaluation plan, concluding that it had successfully attained its numerical targets – 4517 structures analyzed, 3923
registered in the Protein Data Bank, 403 patent applications, and 4195 articles (MEXT,
2007). In addition, one of the studies produced through this project had been cited morethan 2000 times (Institute of Physical and Chemical Research (RIKEN), 2008).
‘The project has, in quantitative terms, sailed along’, commented an article in Nature(Cyranoski, 2006). Here, however, lies a mystery: negative assessments broke out inDownloaded from sss.sagepub.com at University of Tokyo on March 18, 2016

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Fukushimascientific journals and major newspapers during and after its completion; some scientists
questioned the authenticity of the numerical target (Oshima, 2007), while others expressed
their frustration with the project’s domination of the protein science budget and monopoly
over one research institute’s grants (Arata, 2008, 2010; Ikura, 2008). An influential newspaper published an article questioning the idea of such a big biology project (Nakamura,2007), and drug companies were reportedly frustrated about allegedly poor results that did
not sufficiently contribute to drug discovery (Anonymous, 2007, 2009).
One of the most damaging criticisms, making an impression on the concernedinternational community, was the article in Nature cited above. There, Kurt Wüthrich,
the Nobel Prize winner for developing a method to analyze protein structures throughNuclear Magnetic Resonance (NMR) spectroscopy, was quoted as saying, ‘It became aone-man show with 40 NMR machines – there is no knowledge.’ Another researcher
condemned the project as having analyzed only ‘junk proteins’ (Cyranoski, 2006). The
prevalence of such negative evaluations is even seen online in the automatic tag of shippai (failure) that turns up when one looks for tanpaku (protein) 3000 in Google.
The mystery that this article tries to solve is the cause of the impressive asymmetry
between the apparent success of this project in terms of it attaining its official targets andthe subsequent burst of failure discourse.
This article follows the development of this project from the early days of its conception in the 1980s to the period after its completion in 2007. At focus is a particular
dynamic of expectations raised by a variety of groups concerning a then-emerging direction of research called structural genomics, an omics approach to the study of protein
structures. This article will argue that behind the rhetoric of failure concerning this project lie a number of mutually related factors, namely: (1) inter-institutional dynamismthat radically changed the political and research landscape during the period; (2) the
highly controversial nature of this new research topic, which continuously produced
schism within and without the concerned research communities; and (3) the international
context in which this project was embedded.

Theoretical framework
My first task is to sort out how a project can from its beginning be dubbed a failure.
Unless the evaluation comes from a clear failure of a project to meet its own goals, theorigin of such failure discourse should be sought in the socio-technical context in which
it is embedded. In pursuing this, the dynamics of expectations are pivotal (Borup et al.,2006; Brown et al., 2000; Fortun, 2008; Milne, 2012; Van Lente, 1993).
Expectations bring with them emotional connections to hope and hype (Berube, 2006;
Brown, 2003); these can even be formulated as Gartner’s ‘hype cycle’ – a simple diagram
illustrating a sharp rise in expectation, followed by its inevitable fall, and leading to amore moderate plateau – in currency in the business world (Gartner, 2012; Pollock andWilliams, 2010; Van Lente et al., 2013). Although the Gartner hype cycle may be too
simplified (Borup et al., 2006; Rip, 2006; Van Lente, 1993), importantly for my purposes
it identifies disappointment as an integral part of expectation dynamics. However, theoptimism in the model about recovery from the bottom of disillusionment misses the profound consequences that such disillusionment may produce (Borup et al., 2006). Previous

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Social Studies of Science 46(1)studies have discussed such issues in terms of the difficulty of regaining trust once expectations are betrayed (Brown, 2003; Martin, 2002), the preventive measures taken against
such risk by means of legal control (Tutton, 2011), and researchers’ efforts to overcome
disappointment through more radical research practices (Michael et al., 2007).
In the wider context of the development of projects, multiple expectations in theearly stage should be coordinated or ‘funneled’ (Law, 1986; Van Lente, 1993: 140)2
into ‘incremental trial and error learning’ (Collingridge, 1992), with the use of entities
such as ‘boundary objects’ (Star and Griesemer, 1989) and ‘ideographs’ (McGee,
1980; Van Lente, 1993) to nurture the ‘collective expectation’ (Konrad, 2006), whichis to be materialized by ‘selectors’ in the arenas of expectations (Bakker et al., 2011).
Summarized as such, the sources of the failure discourse around the Protein 3000
Project as part of a disappointment dynamics are likely to lie inconspicuously somewhere in this process because the issue is more about unfulfilled expectations than afailed project, per se. In this article, I will highlight three factors that I believe to havebeen instrumental.
One factor concerns a problem that I call ‘structural exclusion’. When one expectation
gains momentum, others – in the form of both expectation and social groups – may bemarginalized or excluded unless their voices are properly subsumed or compromised
with those in the mainstream. Collingridge (1992) and Williams (2006) have pointed
out both the need and the danger of excluding certain social groups or expectations, if
in a rather cursory manner; however, I will fully credit the dynamics of exclusion as
being an important issue in relation to the dynamic of disappointment, which previous
works have failed to explore thoroughly. My use of the adjective ‘structural’ signifies
that in the following case, this process is intrinsically related to inter-institutional
dynamics that enlarge the gulf between what is excluded and what is not – which is the‘prime suspect’ in the prevalence of the failure discourse under discussion.
Related to this, the second issue concerns the failure of the boundary object. Unlike
the ordinary success stories about it – about the subtle balance needed between allowances for multiple and often contradictory interpretations and the value of sustaining aloose unity among them (Duncker, 2001; Duncker and Disco, 1998; Star and Griesemer,
1989; Stemerding and Hilgartner, 1998), I will examine the condition when such ‘magic’is lost or has turned ‘black’ or malignant. This possibility is immanent in the original
concept of the boundary object because its working hinges upon interpretive ambiguity,which potentially causes trouble. In the spectrum from benign (hence successful) boundary objects to disputed issues and uncoordinated actions, I claim there is a certain
in-between condition where an entity may work like a boundary object on the surface,although it is actually causing serious schisms. I label this an ‘anti-boundary object’.
An anti-boundary object carries a capacity to foster collaboration in one dimension,
but may work schismogenetically (Bateson, 1972) in another. Hence, I introduce theprefix ‘anti-’, partially inspired by entities such as anti-proton or anti-matter in the lightof their negative qualities compared with their more common counterparts. In addition,
the object can be regarded as manipulative in a sense of hiding schisms occurring in one
context to reach consensus in another, which I metaphorically compare to entities suchas fallen angels or even the anti-Christ. This notion is instrumental in highlighting
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success and to causing dissatisfaction among those who took it seriously, hence aiding
and abetting the prime suspect of structural exclusion noted above.
The third factor was the urgent sense of ‘international competition’ in which the project
was embedded. Any large international project is both collaborative and competitive.
Competitive aspects on the international stage, however, have received less attention thanissues such as organizational style or methods of collaboration in previous studies on big
science (De Solla Price, 1965; Galison, 1992), management of large technical projects(Collingridge, 1992; Disco and Van Der Meulen, 1998), or big biology (Davies et al.,2013; Parker et al., 2010; Vermeulen, 2010). The prehistory of the Protein 3000 Project –including contexts such as the trade war between Japan and the United States in the earlydays of the HGP – should prompt attention on competition, as the sense of urgency to win
the race may have led to further difficulty in coordinating heterogeneous expectations, thus
accelerating the exclusion process further. In addition, an intriguing side-effect was the‘flexible implementation’ of the big science project to win the international competition,
contrary to common arguments about big science projects being implemented in fixed andrigid ways (Collingridge, 1992; Vermeulen, 2010). This unusual ‘flexibility’ may haveraised expectations, even during its implementation, eventually adding another layer ofdisappointment on top of those already caused by the two other suspected factors.

Background
Structural genomics
In addition to my theoretical framework, two continuos in the pivotal role in the following narratives should be pointed out. One is about the controversial nature of the very
research topic – structural genomics – a chiasmic product of translating the idea ofgenomics to the realm of structural biology. There are two fundamental problems to thisnew trend, namely, (1) the difficulty of applying an ‘omics’ approach to protein structures and (2) the question of the seemingly endless diversity of proteins. In contrast withanalyzing protein’s amino-acid sequences – usually dubbed as proteomics (Chee andClancey, 2013; Lee, 2015; MacKenzie et al., 2013; Twyman, 2004) – the diversity ofprotein structures has produced the unique world of structural biology – based upon
X-ray crystallography, resisting a high-throughput approach (Brenner and Levitt, 2000;
Goldstein, 1998; Montelione, 2001).
In recent years, the rise of NMR spectroscopy has been considered a solution forachieving high-throughput analysis of protein structures. NMR was invented in the
1950s for detecting how molecules bind with each other through generated magnetic
resonance (Blume, 2003; Lenoir, 1997; Morris and Travis, 2002). In the 1980s, Kurt
Wüthrich and Richard Ernst developed the method of applying NMR to macromolecular
protein analysis, an accomplishment that secured the former the Nobel Prize in 2002
(Suea et al., 2005).
NMR does not require crystallization of proteins, a feature for which Myers (2008: n.
25) records X-ray crystallographers’ jokes that branded its ad hoc nature as ‘voodoo science’. Its drawback, however, is its limited analytical capacity; it is restricted to analyzing
only the parts or the ‘domains’ of a single protein (Twyman, 2004; Wüthrich, 1986).

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Social Studies of Science 46(1)As for the conundrum of seemingly endless variations of protein structures, Chothia(1992) proposed an innovative theory of protein folding that reduces it to elementary‘folds’ or structures and their combinations. Although his early estimation of 1000 folds
was later increased, his article opened the door to the omics approach to protein structuresby limiting analysis to elementary structures, the rest to be done with computer simulation. Thus, ‘the determination of as few as 10,000 new protein structures would provide
enough information … to model almost all the protein universe’ (Bonanno, 1999: R851).
The idea of extending the genomic approach with these two innovations – NMR and
Chothia’s theory – prompted the rise of ‘structural genomics’, the omics approach toprotein structures, which took shape toward the end of the millennium. As Gaasterland(1998) explained, it is ‘bioinformatics in the driver’s seat’ (p. 625), colored with a discourse of a revolutionary future (Gershon, 2000; Hol, 2000).

Institutional backgroundThe second continuo to be noted is the institutional background. RIKEN, the official
acronym of the Japanese title for the Institute of Physical and Chemical Research, is themain battlefield. Since its establishment in 1917, on the model of Germany’s Kaiser
Wilhelm Institute as a national flagship research institute, RIKEN’s fortunes waxed andwaned until its revival in 1958,3 as one of the strategic moves of the second institutional
protagonist for this article, the Agency of Science and Technology (STA).
STA was established in 1956 as the extra-ministerial board of the Ministry ofInternal Affairs for the purpose of the coordination of large-scale science policy,
including nuclear energy, space science, and oceanography (Anonymous, 1986;
Watanabe Memorial Foundation, 2009: 4). Their new budget scheme, called theSpecial Coordination Funds for Promoting Science and Technology (shinkô-chôseihi), has been instrumental in launching big science projects (Watanabe Memorial
Foundation, 2009: 17–26).
The Ministry of Education, which supervises higher education and research, has been
involved in a jurisdiction dispute with STA concerning its big science orientation and
RIKEN’s position in science policy. In response, STA transformed RIKEN by creating aseries of time-bound centers, in contrast with the more traditional headquarters of RIKEN
in Wako City, Saitama, with its tenured researchers in about 50 laboratories (hereafter,the ‘Wako RIKEN’). This made RIKEN more directly instrumental in executing STA
science policy after the 1980s. The inter-institutional politics is also pivotal for understanding the zig-zag itinerary of the earlier project plan that would become the final
Protein 3000.
The following sections describe the development of the Protein 3000 Project from its
inception by the Wako RIKEN biologists in the 1980s to its actual enactment and theaftermath in the 2000s. I identify three distinctive phases in the development of the project. In each phase, the composition of the main characters and their expectations changed
almost completely, the changes caused by various levels of inter-institutional conflicts,
growing controversy about the meaning of the emerging structural genomics, and theinternational collaboration and competition that gained momentum as time passed. All ofthese entangled elements resulted in not only discontinuity from the previous phase but

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Fukushimaalso voices of disappointment, misunderstanding, and even indignation at various levels.
This eventually led to the prevalence of shippai (failure) discourse, despite the fact thatthe project was seemingly successfully launched and had even attained its initial goal –important after the preceding ‘defeat in the genome’.

Research method
The research on this project was divided into two phases. The preliminary part, from2007 to 2009, was part of an ethnographic study of an antibiotic laboratory in RIKEN(Fukushima, 2013) on the development of natural products chemistry and chemical biology. During this period, I conducted pilot interviews with the participants of the earlier
Protein 3000 in the lab. This enabled me to identify the outline of the issues as well as
key persons to be accessed in the following phase.
The main research took place from 2010 to 2013; it was based upon semi-structured
interviews with 17 central actors, concerning both their roles in the project and theirgeneral views about such project at large. These were scientists and officers, selectedfrom the aforementioned pilot studies, who played leading roles at various levels, fromthe project’s planning to its implementation in and out of RIKEN. The interviews were
supplemented with archival reviews of journal articles, policy documents, proceedingsof the project, newspapers, and so forth. Attention was paid to RIKEN’s pivotal role in
the project, as the majority of the later criticism more or less concerned with the institute.
All interviews were recorded and then transcribed. Although I made a great effort to collect key policy documents, quite a few have been lost owing to the present ministry’s
repeated restructuring and moving.

Phase 1: The birth of the idea of ‘the NMR Park’
In the 1980s, the X-ray facilities in KEK (High Energy Accelerator Research Organizations;cf. Traweek, 1988), supervised by the Ministry of Education, and RIKEN’s constructionof SPring 8 (Super Photon ring-8 GeV), the world’s largest radiation facility (Interview6), marked the consolidation of research infrastructure for protein science. By way ofcontrast, two laboratories were to be noted for the introduction of NMR machines
specifically for protein analysis: one at the University of Tokyo first introduced thecutting-edge superconductor NMR by Bruker Ltd. in 1976, while another at the Osaka
University purchased NMR equipment in 1980 (Tasumi, 2006). The former laboratory
produced the later leaders of the Protein 3000 Project, while the latter exerted extensive
influence on the whole community of structural biologists.
At the Wako RIKEN, Takehiko Shibata, a specialist in the homologous recombinationof DNA, took office in 1985 and launched the Bio-Design Project to promote the life
sciences and to raise their status there; this involved all 10 of RIKEN’s genomics andstructural biology laboratories. In 1993, Shibata invited Shigeyuki Yokoyama – later oneof the general leaders of the project – to RIKEN to establish a structural biology laboratory (Interview 4). Yokoyama was a graduate of the above-mentioned lab in Tokyo, specializing in DNA–protein interaction using NMR, a rare specialty because of NMR’s
limited capacity at the time. In the early 1980s, Shibata had already been impressed with

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Social Studies of Science 46(1)Yokoyama’s claim for the merits of NMR in analyzing the ligand–protein interaction
within solutions, which could solve Shibata’s own research problem (Interview 4).
Another proposal from Yokoyama also prompted Shibata to introduce NMRs:
We also thought that we could gain support if we had an international NMR center open for use
throughout the country [as proposed by Yokoyama], because it is hard to have and maintaincutting-edge NMR machines in a lab or even in an institute. (Interview 4)Thus, in 1994, Yokoyama launched the idea of a comprehensive analysis of the elementary structure of proteins using ‘100 NMRs’ in the Bio-Design Project. The official historiography of RIKEN comically describes the shock of a senior chief researcher, whosuspected that Yokoyama had lost his marbles (RIKEN, 2005); such a concentration of
NMRs in one place was unprecedented both within Japan and elsewhere. Yokoyama later
explained at least two reasons behind his exorbitant proposal: first, Chothia’s (1992)
article on elementary structures of proteins convinced him of the feasibility of a comprehensive analysis of protein structures (Oshima et al., 2002b: 867). Second, there wasa twist in the numbers of NMRs that he wanted:
I said eight NMRs, not 100, but they [the physicists in the Wako RIKEN] asked if I was sane.
They said that even if we had eight NMR machines of 600 MHz, the total size is 2.4 GHz or so,which, they said, would not lead to new science. (Interview 19)

The idea of 100 NMRs was instigated by nuclear physicists in the Wako RIKEN, whowere accustomed to big facility proposals in terms of accelerators: Shibata and others
testify that ¥10 billion (US$100 million) was the basic unit of a big proposal there(Interviews 4, 11). Yokoyama emphasizes that the idea of simultaneously purchasing
several machines of similar size was then novel:
Even Wüthrich later asked me what I was going to do with the machines when world NMR
researchers rarely bought even two of the same size. But in reality, after we had the NMR
facility here, similar things happened in the rest of the world. … Our plan was ridiculed as ‘theproject of buying NMRs’, but in fact there were rapidly expanding needs for protein analysis,
so we had to respond to them. (Interview 19)

The 100 NMRs proposal obtained approval in snowball fashion, swiftly ascending theladder of RIKEN’s and STA’s bureaucratic machineries (RIKEN, 2005). STA needed a
big-budget project to consume a surplus budget after the completion of the nuclearpowered ship Mutsu (Interviews 4, 11).4 An add-on booster for the NMR project was theidea of sequencing the whole protein structure of Thermus thermophilus for medical
purposes. Thermus is a gram-negative Eubacterium that resists high temperatures –discovered in a hot spring in Japan – that produces easy-to-crystallize proteins. Seiki
Kuramitsu, a biochemist from the Osaka University, had long nursed the idea andYokoyama, soon after becoming acquainted with Kuramitsu in 1995, adopted it;
Kuramitsu was later one of the main leaders of the Protein 3000 Project, along with
Yokoyama and others (RIKEN, 2005; Interview 18).

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Rising expectations for ‘the Park plan’
In the process of this administrative legitimation, two contradictory tendencies gradually
emerged: the growing expectation for the communal use of NMRs and the plan to go
beyond such a scope. The NMR plan, later named ‘the NMR Park’, was intended to be acommon facility open for international use (Interview 4; cf. Vermeulen, 2010). The
spread of the news of this plan elicited various reactions ranging from wholehearted
approval to restrained skepticism. Shibata summarizes the atmosphere of this stage of theplan:Thus, there was widely shared support for the idea of such facility, shown for example in thereports in the Nature journal around 1997 [sic]. What was supported was the facility’s being
open to international use. And they also supported it because this facility is also contributing toenhance Japan’s presence in this field. (Interview 4; cf. Swinbanks, 1996)

A number of people commented on the international support:
In fact, researchers both in Europe and the US strongly welcomed the idea, because they could
make use of this precedent: ‘Japan spends such money, so should we.’ (Interview 3)
So at that time, researchers in India, for instance, were enthusiastic about the plan, saying ‘Ifthere is such a plan, we are keen to participate in it. Let us use them.’ Now the Indians are richenough, no need for it any more, though [laughter]. (Interview 7)

Domestic reaction was more varied. Certain expectations seemed to have risen among
younger generations of researchers:[Admitting the later criticism on the project] At the moment, among the younger generation,
there was surely approval of the plan. … I don’t believe that those who were not established intheir academic careers … had only bad impressions of [the Park plan for] developing anenvironment where you may make use of a machine of 900 MHz with only the slightest effort.
(Interview 8)More senior NMR specialists had mixed reactions:
When it [the Park plan] was announced … their [the attendants of the NMR seminar] reactions
were ‘Wow!’ or ‘That’s great!’ … Well, the meaning of ‘that’s great’ was probably they didn’t
believe that it would actually take place. (Interview 10)

Despite a few skeptical voices, these various witnesses point to the general rise of expectations among NMR researchers. However, things turned in an unexpected direction
when a couple of new factors came onto the scene.
In sum, this phase was important not only for the project but also for establishing the
research infrastructure urgently needed for structural biology, which, at that time, lagged
far behind that of other countries. STA was also redirecting its policy toward newly
emerging biological fields. Its attention to the pivotal role of RIKEN in actualizing a new

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Social Studies of Science 46(1)direction of research coincided with a bottom-up movement of biologists promoting
emerging biological fields and a brand new tool, NMR. Thus, a happy coincidence
occurred in the meeting of goals of some cutting-edge biologists and big-science-oriented policy makers, which created expectations of communal NMRs. But this accidental amity would soon disintegrate, and hopes would turn sour.

Phase 2: Transformation of the NMR ParkIn Phase 2, the subject of the project was radically enlarged both in policy and in institutional
context, where the process of funneling the multiple expectations was affected by a drasticchange in the institutional configuration. The nexus of the project would eventually movefrom the Wako RIKEN to the newly emerging Genomics Science Center (GSC), RIKEN,
with a new main character on the stage: Akiyoshi Wada, introduced above in connection with
Defeat in the Genome. In this process, the negative effects of excluding various expectations
gradually came to the fore. This development was also pursued with the sense of urgency
vis-à-vis a rapid international development concerning patents on protein structures.

The rise of the GSC, RIKEN
The initial trigger for this radical change from the earlier plan was an inspection by the
Ministry of Finance, which demanded two things. First, it wanted RIKEN and STA towrap up their mushrooming individual life science projects. This was during the time
when the HGP was challenged by Craig Venter’s Celera Genomics in 1998 (Venter,2007). There were a number of HGP-related projects in Japan, such as four national
teams participating in the HGP, including one from RIKEN (Shimizu, 2000), themouse cDNA project in RIKEN’s Tsukuba Center (RIKEN, 2005: 329–351), and the
NMR Park plan. In response to this demand, Akito Arima, ex-Minister of Education andlater the President of RIKEN, commissioned for the task his old friend, Akiyoshi Wada,
who had retreated to a small research institute after retiring from the University ofTokyo (Interview 20). Wada responded by restructuring the research as the ‘New Life
Science Plan’, under the banner of ‘omics space’. This was designed around a schematic
diagram situating genomic and post-genomic life science in terms of five layers: genome,transcriptome, proteome, metabolome, and phenome (Wada, 2008: 67–68). A former
officer of STA who later joined RIKEN’s managing board testifies to his personal
impression of the impact of Wada’s perspective:
The greatness of Prof. Wada is to situate protein research within the whole structure of various
omics. So far as I know, there was no one else who did it at that time. I truly believe that Prof.
Wada is a great person. … At first he made clear the whole hierarchical structure of omics, andthen underscored the importance of attacking on all these levels with quantitative data analysis,
which, he declared to the world, was the strategy of life science to come. This is extraordinary.
And we now know after genomes, it’s proteins. Proteome. (Interview 14)

Eventually, Wada’s comprehensive omics plan led to the establishment of the GSC in the
Yokoyama RIKEN in 1998 (RIKEN, 2005). Seen from the Wako RIKEN, however, it
looked as if their own plan was alienated:

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There were cases in which our proposal did not pass in RIKEN’s managing board. … We
developed a plan for a collaboration team with GSC … but eventually it was not accepted. …
In short, it seems to us that Prof. Wada did not want to be inconvenienced by the ancient regimeof RIKEN, which he may have thought could become annoying. (Interview 4)

Behind this growing rift between them, the former STA officer quoted above corroborated the long-term intention of STA’s intervention into the direction of the GSC
as playing a role in policy objectives (Interview 14). Later, Wada himself seems tohave acknowledged the character of his center as ‘running alone’ vis-à-vis the old
Wako RIKEN:
There was an interesting structure, in terms of RIKEN’s managing board. They came from
STA, and when we established GSC, in STA I had my old friend …, who thoroughly supported
GSC’s running alone. And [citing a few names] STA sent all their aces to GSC, so that’s maybe
the reason why GSC looked like an independent fortress [shiro] against the Wako RIKEN.
(Interview 20)5

Structural genomics and its discontents
Such inter-institutional conflict was accompanied by turmoil about the rising currencyof the idea of structural genomics, partly related to a second thing that the Ministry of
Finance wanted for RIKEN: to prove the validity of such a large facility in an international context (Interview 11). Thus, Yokoyama and others traveled to the United States
and tried to impress their counterparts:
We went to a meeting to discuss NMR facilities in the US, and our story about the same 100
machines on line was printed and presented as if we were about to launch this, and I heard
afterwards that the US side realized that they would face a serious problem if they were caught off
guard. … I heard that there was an ‘NMR Park shock’ in the US. … At that time our copy of theplan we distributed there circulated throughout the US where it became worn out. (Interview 19)

As if corroborating this alleged ‘shock’, the official chronology of the International
Structural Genomics Organization (ISGO, 2013) traces its history from Yokoyama’s
1995 proposal at RIKEN first, followed by a series of international reactions, such as theUS’ 1997 New Jersey Initiative and the Workshop on Structural Genomics in the Argonne
National Laboratory. The latter institutionalized the name of the international project as‘structural genomics’ (Terwilliger, 2000).6 These events were followed by the Nature
Structural Biology special issue, which was devoted to structural genomics in the UnitedStates (Terwilliger, 2000), Europe (Heinemann, 2000), and Japan (Yokoyama et al.,2000a, 2000b). Meanwhile, in a subsequent conference in Virginia, the ISGO was officially launched and was instrumental in setting a target of 10,000 protein structures to beanalyzed in international collaboration (Smaglik, 2000).
Here, however, the controversial character of structural genomics – eventually as ananti-boundary object – gradually emerged in the shape of suspicion of its basic assumptions by structural biologists. First, the senior NMR experts who Wada consulted as hewrapped up his comprehensive plan – Yoji Arata, Kurt Wüthrich, and other senior
members of NMR research – expressed their skepticism about structural genomics.

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Social Studies of Science 46(1)Among others, Arata, another pioneer of NMR research on protein structure, wholaunched the NMR Society of Japan in 2002, kept his distance, compared with
Wüthrich’s more active involvement in the Park plan per se, which can be seen in theformer’s general disbelief in the validity of genomic approach at large: in fact, Arataboasted of his more time-consuming method of determining the large structure of
immunoglobulin of 150,000 molecular size – which even Wüthrich’s method could not
attain – by labeling strands with 13C, which he believed is more reliable than othermethods discussed above (Interview 7)
Although not as blatantly, other leading structural biologists in Japan also voiced theirskepticism about structural genomics, highlighting fundamental differences between
their approach and that of Yokoyama (Yanagita et al., 1999). In further discussions in
2002, a leading bio-informatician openly questioned the basic assumption of structural
genomics: namely, the idea that the functions of proteins could be understood by comprehensively analyzing their structures (Oshima et al., 2002b). Even Yokoyama did notappear to be fully convinced by the international trend: he expressed discomfort about
the Virginia conference that was dominated by bio-informaticians such as John Moultand Chris Sander from the United States, who seemed to him to disregard the need to
improve high-throughput machinery for structural analysis (Oshima et al., 2002b).

The urgent issue of patents
Despite such smoldering suspicions, the perception of the international situation caused
the Japanese participants at ISGO to realize the impending threat of the US move (cf.
Meyers et al., 2000). As Yokoyama reflects,
Then the story was that the PSI [Protein Structure Initiative] in the US was about to launch. At
that time, it was said that patents could be acquired for protein structures. And it was the time
when the US was securing patents for cDNA, so we were alarmed that it will be lethal if the US
monopolized the patents of protein structures. … It was a bit hypocritical of the US to insist on
making the information [of protein structure] open to the public immediately because it is only
the US that has the industrial capacity to make it profitable. We strongly countered that Japan
did not have such capacity while we are doing this project through the support of the state, so
we opposed the idea of immediate opening of the data. (Interview 19)

The momentum, especially because the international competition, prevailed over thesuspicions among structural biologists, and there was soon a push toward the final
Protein 3000.
In sum, in this phase, the plan for the NMR Park, a vague product of researchers’
dreams, rapidly transformed into something utterly different. Inter-institutional struggle,
for instance, was pivotal in transforming the center of gravity for the project, when STA
showed its commitment to promote the plan as national policy in the midst of international competition. This eventually marginalized the promoters of the earlier plan for the
NMR Park. The changes were accompanied by a growing schism among leading biologists regarding the very significance of structural genomics, even as, ironically, the new
genre of research gained momentum on the international stage, accompanied by growing

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competition between Japan and the United States. Hence, the emerging ‘structural
genomics’ started to show its peculiar character of both creating schism among biologists
domestically and providing a space for collaboration internationally, beginning tobecome a puzzling anti-boundary object.

Phase 3: Protein 3000 as national flagship project
In Phase 3, until the actual launch of the project in 2002, further institutional changes
took place that again radically changed the landscape of the project. The monopoly of the
RIKEN-STA alliance was disrupted to open the project to a broad array of Japanese
researchers. In this process, a fatal blow was struck against the idea of the NMR Park,
while the plan to analyze 3000 protein structures was finally staged as the central agenda.
The changes had a decisive impact on the nagging criticism about the project that had
persisted even after its launch.

Changing meaning of the projectTwo important administrative events should be noted. The first was the Millennium
Project, launched by the government in 1999, to promote important national scientificprojects for the new millennium. This big-budget scheme finally afforded the comprehensive plan a final go-ahead as a package (Interview 14). The second event was a largescale reorganization of the government offices in 2001, in which there was a merger
between the competing STA and the Ministry of Education to become the Ministry of
Education, Culture, Sports, Science and Technology (MEXT) (Oda, 1998). The project
became shared across research communities in Japan, rather than being a RIKEN-STA
monopoly: university researchers as well as traditional crystallographers and even bioinformaticians became eligible for grants (Interviews 16, 19).
Why was the target 3000 protein structures? Yokoyama’s collaborator details its
background:At that time, there was a sort of policy catch phrase, ‘the scientific and technological nation’[kagaku gijutsu rikkoku], and Japan wanted to bear 30% of the world’s science and technology.
A bit high-handed if looked at now, but at that time, in response to ‘the defeat in the genome’,
the catch phrase circulated in the world of planning the budget. … And at that time the domainsof proteins were said to be 10,000, even if it is more now. Thus, 30% would mean 3000.
(Interview 16)

Although this target number itself would later invite criticism, even from its promoters,
as more political than scientific (cf. Arata, 2008; Oshima, 2007), Yokoyama claims thathe then thought it was feasible. Thermus thermophilus has only 2000 genes, and it was
believed that it could contribute half of the 3000 protein target (Interview 19).
A thorny issue was how to allocate 3000 targets among the various participants. Besides
RIKEN, there would eventually be eight different hubs, divided according to topics ranging from development to metabolism, involving both universities and research institutes(Oshima, 2007).7 After tough negotiation between Wada’s GSC and crystallographers in

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Social Studies of Science 46(1)universities, only 500 proteins in total were finally given to these hubs, as they claimed it
was the limit for them as a whole, and the rest stayed at GSC (Interviews 16, 19).

The death of the Park planThis enormity of the task imposed upon GSC – analyzing 2500 protein structures in 5 years– further brought about what was probably the most controversial decision concerning thenature of the project: GSC decided to restrict the use of 40 NMRs, which had been rather
unexpectedly provided to GSC, for use in the project, making them off-limits to outsiders.
This decision symbolized a complete break from the original conception of the NMR Parkwith open access, and this decision aroused a storm of indignation from the concerned
NMR community. Here are comments from the original Bio-Design side on the decision:
It was far from what I thought ideal … The reason is, it did not become a center that everybody
wanted … I mean, open use. And if it had been open, there would have been a lot of visitorsfrom all over the world. And that would have facilitated the determination of new structures
faster than the comprehensive research on elementary structures … Well, I tried to persuade
them to open one or two machines, but was not accepted. (Interview 4)

A noted structural biologist also describes the NMR community’s reaction:
Nobody could use them. And that was the point most severely criticized by NMR researchers
about Protein 3000. Even Dr. Shibata could not use them [because he wouldn’t have wanted touse them ahead of other researchers]. (Interview 10)

Wada, then a director of GSC, also witnessed the reactions from leading figures of the
NMR community:
Prof. Arata [senior NMR specialist] demanded of me to make the NMRs open to university
researchers. Behind him there were a lot of NMR researchers, so I suppose there should havebeen pressures from them too. … What Wüthrich repeated to me was ‘You talk about NMR
Park. A park is the place where anyone can enter. But what about it now? It is not a park, it’s aprivate house.’ (Interview 20)

From the implementers’ side, the story seems more complex. For one thing, the legal
basis for the project became what is called ‘the intra-ministerial budget’ [naikyokuyosan] within the merged MEXT. It stipulated that the contract was ‘commissioned’ by
the government to the contractors, with no openness allowed (Interview 19). The former
officer of STA clarifies the policy makers’ viewpoint:
If I had heard the plan of the 100 NMRs [Park plan] and Protein 3000, I would not have bought
the 100 machines idea. … [discussing the brain research center in RIKEN as an example] when
we heard the discussion of the future of brain research, it was our role to make clear the concrete
plan that could be attained in five years. The planning based upon the ideas and intentions
summarized by researchers are totally different from formulating the research project, having
significance as national policy, from all these plans. (Interview 14)

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Yokoyama also points out it was a matter of survival for RIKEN, which was responsible
for this national flag project and which could not afford to fail (Interview 19). Wada
stresses the difficulty of managing the project had it been open:
It would have been a big problem if we had opened 40 NMRs for international use. … As I haverepeated, the idea of GSC was a factory of mass production of biological data. … So if peoplecame and said ‘This data is mine, this data is mine’, then it would have been uncontrollable.
(Interview 20)

In sum, this phase solidified the irreparable schism between those within the scope of the
project and those who were eventually excluded. The once-in-a-century reorganizationof the ministerial structure fundamentally changed the nature of the project from that of
STA-RIKEN to the all-Japan project. The related legal stipulation almost completed theprocess whereby the promoters of the earlier plan were excluded, and voices of negative(even emotional) reactions ensued from the marginalized. At the same time, the general
haste to launch the project, caused also by accelerating international competition, which
was accompanied by the almost impossible task of analyzing 2500 proteins, made theproject vulnerable to various levels of criticism, which betrayed a poor understanding ofwhat the project was all about.

The launch of the project and its aftermath
Thus, we have traveled a long way: the final outlook of the project had left almost no
trace of the earlier image of the NMR Park as open for international use. The headquarters moved from the Wako RIKEN to GSC in Yokohama. The early sympathizers for thePark plan were marginalized, whereas newcomers from various universities and disciplines were installed under the supervision of the new ministry, MEXT. Thus, voices of
discontent rising from the series of exclusions had already accumulated when the project
was launched in 2002.

GSC as super center
The enormity of the task of analyzing 2500 protein structures made GSC a sort of super
center, a concept that Hilgartner (2013) writes was avoided in the case of early HGP in
the United States. For attaining its goal, GSC had to maximize both the crystallographic
capacity of SPring 8 and the 40 newly purchased NMRs. GSC rapidly hired approximately 300 new staff, post-docs, and technicians in 19 research units. For speedy analysis, factory-like pipelines were needed, starting from finding genetic sequences fromvarious sources, followed by systematic expression of proteins, which were then sorted
according to crystallizability, either for SPring 8 or for NMRs (Interviews 3, 9, 12, 15).
Unlike the fully computerized sequencing in the case of genomics (Stevens, 2013;
Venter et al., 1996), automation was only partially available in certain parts of crystallographic procedures at SPring 8 (Interviews 5, 15, 18). In contrast, NMR was morelabor-intensive (Triendl, 2001) and new members, stationed to individual research units,were obliged to process compartmentalized assignments (Interviews 3, 9). Through thisDownloaded from sss.sagepub.com at University of Tokyo on March 18, 201622

Social Studies of Science 46(1)process, the meaning of structural analysis also changed because the researchers could
not find a sort of periodic pattern of such elementary structures. They changed to simply
annotating each of the collected structures (Interviews 9, 17, 18).

New expectations for drug discovery?
There were changes to the project even after its launch, in response to new expectations
that arose during its implementation (contra Collingridge, 1992; Vermeulen, 2010). Thisphenomenon was partially caused by the smooth attainment of the target number in thefirst half of the project period, after which officials set new expectations around drug
discovery. As Yokoyama witnesses,
We realized at the time that after the intermediate review, such an explanation as ‘thesuccess of this project leads to drugs’ was in currency [among policy makers]. … In thecase of the HGP, everybody knows that observing a base sequence does not make you thinkof drugs, but in the case of proteins, unfortunately, people may think that the determinationof the active site of protein may lead to drug design, and if so, we had to take it seriously.
(Interview 19)

He also points out the international factor:
The meaning of the project changed because of the change in the American situation. The US
was already in the production phase before we started on Protein 3000 … and this is why wewere in a hurry. But then what the US would do after, well, it would be about disease. … So weargued that things related to disease should be done. (Interview 19)

This change, however, caused difficulties because mammalian proteins, the targets ofdrug discovery, are usually harder to crystallize than those of Thermus thermophilus thatthey had previously used (Interview 12).
In addition, the supervising committee became stricter about monitoring numericaltargets, so that the final year was marked by problems in determining analyzable proteins,because generally more complicated ones remained (Interviews 10, 12, 15).8 On thispoint, Kuramitsu, co-director with Yokomaya above, rather cynically reports the reactionof his friends abroad on the unusual ‘flexibility’ of the execution of the big project like
this:
Well, it was something foreigners often said to us. Abroad, once a 5-year project is launched,
they first make the goal, and when they decide to do it, the budget and other things will be given
as decided. In Japan it is interesting to find that you change your direction and the budget canbe decreased. Well anyway, it’s awful. (Interview 18)

The aftermath
In 2007, MEXT’s Life Science Committee concluded that the project had successfully
attained its numerical targets. In terms of equipment, their report enumerates numbers
such as 99 NMRs and 226 X-ray detractors, the development of beamlines at RIKEN’s

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SPring 8 and at KEK’s Photon Factory, technological innovation with regard to expressing proteins, a micro-crystallization manipulator, automatic X-ray detraction, and so on(MEXT, 2007).
However, there were critical voices throughout. In 2002, an economic journal published an article questioning various aspects of the project, such as MEXT’s managing
capacity, the scientific justification of 3000 targets, and the quality of the collected data
(Masuda, 2002). After completion, the chair of the project’s Promotion Committee
revealed in an interview his frank view on the merits and demerits of the project, including the political nature of the target’s being set at 3000. The article also compiled existing
criticisms, including the lack of patents, data registration delays, human resources, andexcessive costs (Oshima, 2007). Referring to this interview, a well-known biologist, acting as the head of the Life Science Museum, launched a critique of the project in an
influential daily newspaper, comparing it with the Cancer Genome Atlas Project in the
United States and condemning it as being hastily conducted without scrutinizing its scientific meaning (Nakamura, 2007; cf. Isaji, 2009). Despite Wada’s (2007) swift rebuttal,
her critique ignited heated controversy on the issue, primarily online.
The following year, a protein research journal published a special issue on the project (Tsukihara and Nakamura, 2008), in which a number of articles criticized issues
such as the uneven distribution of grants and the project’s economic accountability(Ikura, 2008; Hakozaki, 2008). Yoji Arata – then becoming one of the most vocal critics of the project – was unrelenting: he denounced the project for failing to innovate
NMR-based protein analysis and for having no impact on either science or drug discovery. He attributed this failure to the general malaise of Japanese science policy,
which he characterized as opaque and lacking in legitimacy (Arata, 2008, 2010;
Interview 7). This accusation echoes Wüthrich’s in the Nature article mentioned earlier(Cyranoski, 2006). Both promoters and critics acknowledged that Wüthrich’s negative
perception of the project as having created ‘no knowledge’, and an additional remark
about ‘junk proteins’ by another structural biologist, seriously damaged the project’s
international reputation (Interviews 4, 8, 19), despite rebuttals by the internationalteam (Yokoyama et al., 2007).
The widespread effect of such controversy is evident in a science policy budget commentary in another influential newspaper in 2009, which introduced the project as an
example of failure: ‘[This project] was meant to develop new drugs by analyzing thestructure of disease-related proteins, but it fell short of answering such expectations’(Anonymous, 2009).

Discussion
The Protein 3000 Project was originally intended to overcome what was called ‘thedefeat in the genome’. From the perspective of Kishi’s book by that name, the Project
should have passed the trial with several factors in its favor: the clear vision on protein
research based upon the idea of ‘omics space’, STA’s determined support for Wada’s
GSC to take initiative in the international community of structural genomics, and theunprecedented scale of a budget that enabled a contribution of more than 30 percent of
the international effort. Understandably, official reports were positive.

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Social Studies of Science 46(1)Expectations marginalized and excluded
Against such a positive evaluation, the possible sources of the harsh criticisms have to be
explained. A first source was the process of funneling and excluding earlier expectations,which was influenced by a series of discontinuous development in inter-institutional
dynamics. The early NMR Park plan was gradually eroded, replaced by a national flagship project in the Protein 3000 project.9 In each phase of its transformation, the centerof gravity also moved and was accompanied by the marginalization of those who werecommitted to the earlier ideal – namely, those from the Wako RIKEN who favored an
open Park, the senior experts of NMR seeking for a new horizon for NMR’s expanded
capacity, and, finally, quite a few of the NMR community who were excluded fromaccess to the 40 NMRs at GSC. A consideration of these changes is essential for understanding such criticism about the ‘opaqueness’ of the planning process (Arata, 2008,2010), as it seems that even the promoters were not able to foresee such changes.

Structural genomics as an anti-boundary object
However, the foregoing explanation leaves questions unanswered. For instance, why did
discourse like ‘no knowledge’ or even ‘junk proteins’ prevail in public journals like
Nature (Cyranoski, 2006)? Why was it claimed that the project was of no use to drug
discovery (Anonymous, 2007, 2009)? The second source of the failure discourse, then,seems to have been structural genomics as an anti-boundary object.
One of the impressive idiosyncrasies of this project has been the sharp distinction
between its international positioning as a project of ‘structural genomics’, and its actual
implementation by traditional ‘structural biologists’. The gulf between them can be seenin the comments of a leading structural biologist in the project, who emphasized that the
informational assumptions of structural genomics do not enable an analysis of the subtle
relations between the structures and functions of proteins. He also added that in the
United States, structural genomics and structural biology are different species, segregated in terms of their funding (Interview 10; cf. Oshima et al., 2002a). Corroboratingsuch a gulf were the harsh exchanges between researchers in the United States on the
alleged success of the Protein Structure Initiative (Gerstein et al., 2003; Service, 2002).
Pellegrini (2005) contended that the larger community of structural biologists was dissatisfied with the outcome of the initiative, which dealt only with simple structures incontrast to the heroic efforts of crystallographers in analyzing large macromolecularcomplexes (see Abbott, 2005 on its success).
Not resolving this difference fueled the failure discourse. The expectation and ambition of quite a few NMR specialists were to tackle proteins of a large molecular size by
expanding the limits of NMR. In contrast, the Protein 3000 Project used NMR to analyze
only small ‘elementary structures’, based upon Chothia’s (1992) theory and bio-informational assumptions. In fact, Kuramitsu confirmed that only he and Yokoyama were somewhat faithful to the creed of structural genomics (Interview 18), Wada being added as the
godfather of ‘omics space’ (Interview 20). A GSC unit leader confirmed that it was only
the bio-informaticians abroad who generated various findings using the database(Interview 12), whereas a leading bio-informatician in Japan acknowledged the limited
role of bioinformatics in the project (Interview 17).

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The notion of an ‘anti-boundary object’ is useful for describing this odd situation. In
the project, despite its somewhat misleading appeal to the international community, theconcept of structural genomics worked only in its absence to combine domestic actors:
the majority of the participants from universities did not seem to take this concept too
seriously as their assignments were eventually to determine the structures of a few proteins, compared with 2500 for GSC. Borrowing Schrader’s (2010) argument of the‘phantomatic’ ontologies of the controversial fish killer, it may be tempting to call structural genomics a ‘phantomatic discipline’ whose nature as a discipline is seriously disputed. But structural genomics worked concretely rather than phantomatically, with
contradictory effects; hence, the term ‘anti-boundary object’ is more apt to describe thecomplex situation wherein this genre of research is situated, which eventually led to criticisms such as ‘no knowledge’ and ‘junk proteins’.
Usually, a successful translation between actors by means of a boundary object isobserved in a single dimension, so to speak. In the case above, however, the translation
matters in two different dimensions: one is within the project itself, and the other is in theinternational context. What matters here are the divided functions of the same object –namely, failure in one dimension and success in the other. The success demonstrated on theinternational level is not only misleading (hence, ‘anti-’ in a manipulative and quasi-theological sense) but domestically it may actively give rise to disputes so that it is better for it
to be avoided (hence, ‘anti-’ in the sense of being contrary to creating harmony). Thus,
alternative expressions such as ‘failed’ or ‘misaligned’ boundary object will not illustrate
fully this complex situation as they are confined to a one-dimensional perspective.

The project in the international competition
We can see some of the problems of the Protein 3000 Project if we compare it with thesubsequent Targeted Protein Project (MEXT 2011), which seemingly sailed along without
much ado. There are a couple of reasons for this: one is that the subject of this subsequent
project returned to a more classical concern in structural biology – membrane proteins
and those of large molecular size, which are important as targets for new drugs – without
any further trace of structural genomics therein.
The way that the projects were planned and implemented was manifestly different, as
illustrated by a comment by Yokoyama’s collaborator on this issue:[In the case of Protein 3000] there was not much time to do it meticulously. For Targeted
Proteins, I had been a member of its preparation committee for three years and we carefullycompiled various reports, but in the case of Protein 3000, no time for that. Only one or two
conferences … It was far rougher than now, indeed. (Interview 16)

The ‘roughness’ of the way the Protein 3000 Project was planned is partially attributable
to the urgent atmosphere of the time, when many international issues – such as the tradewar, the HGP, Celera Genomics, fear of the monopoly of patents, and so forth – wereentangled. We have already observed that a sense of urgency dominated its promotersvis-à-vis its international rivals in the various steps of its development. Even at the end,
the rise of expectations of new drug discoveries was prompted by a rival’s perceived
move in that the direction.

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Social Studies of Science 46(1)Persisting repercussions of the project
The immediate above contrast in styles of management reminds us of Collingridge’s(1992) claim concerning the central importance of incrementalism and of trial and error
learning in big projects. However, I doubt that the problem would have been solved even
if Collingridge’s proposal had been practiced during the Protein 3000 Project, and one
final episode may illustrate my point. A variety of NMR researchers emphasized therecent progress of the research on so-called intrinsically disordered proteins – proteins
without proper structure (Chouard, 2011) – which may provide renewed opportunity for
NMR to prove its potentiality. They are chagrinned, however, that new investment into
NMR is now out of the question because of the earlier huge omics-inspired investment(Interviews 4, 7, 8, 10).
Thus, while Wada of GSC praises the value of these ‘data’ for coming generations(Interview 20), an opponent describes the 40 NMRs at GSC as ‘a huge wreckage ofextravagance in the shape of a ghost town’ (Arata, 2010: 161). Similar contrasts can beseen in the life sciences at large, in the differences between traditional approaches andthose based on informational orientations (among others; Fujimura, 1999; GarcíaSancho, 2012; Kay, 2000; Lewis and Bartlett, 2013; MacKenzie, 2003); the tension
between these orientations seems to prevent Collingridge’s solution from being fully
effective in erasing the voices of failure, the difference being apparently almost unbridgeable, at least in this case.

Conclusion
In the context of domestic science policy in Japan and global competition for postgenomic science, the Protein 3000 Project provides rich material for reconsidering thevarious assumptions of diverse research areas. First, this case study demonstrates thatdeveloping a particular policy idea by funneling multiple expectations into a concrete
plan has a darker side of excluding certain elements; such an approach may lead to continuous criticism, resulting in eventual devaluation of the very project itself contra its
attaining the goal. This is especially the case if the funneling takes place haphazardly,
driven by outside events – such as, in this case, changing institutional structures. Thus,
the role of the neglected side of failed expectation, disappointment, and even persisting
frustration deserves further research without being confined to official reports but involving the wider realm of society at large.
Second, boundary objects – which are usually expected to bind heterogeneous elements benignly and loosely in pursuit of a goal – can also have a darker side. The antiboundary object functions with Janus-like faces to bind together at one level, but tobetray at another by creating schisms when it is fully activated.
Finally, the fierce sense of international competition embedded in this project urges
reconsideration about the basic assumptions of recent arguments about big science/big
biology, which have been tilted toward underscoring collaboration when competition
may have larger effects.
This analysis of the sources of a discourse of failure is a good lesson in learning what
not to do in order to avoid the long-lasting aftereffects of the dark side of unfulfilled

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expectations. Otherwise, any project – the product of many dreams – may turn for some
into a haunting nightmare.
Acknowledgements
I thank all the interviewees for patiently answering my questions. I thank Greg Clancey, Boel
Berner, and Geof Bowker for their lively discussions over the draft at various stages of the development of this article; thanks also to Sergio Sismondo and three anonymous referees for theirconstructive comments. Special thanks to Mike Michael, whose detailed comment on the earlier
draft cleared its path to proceed.

Funding
This research was conducted with the support of grants-in-aid for scientific research from theJapan Society for the Promotion of Science, under Grant 23501199 (2011–2013).

Notes
1.

2.

3.

4.

5.

6.
7.

8.

9.

One of the pictures of such ‘blunders’ is the Science and Technology Agency’s (STA) cancellation of the patent granted for Yuzuru Fushimi’s four-color fluorescent labeling in 1984, owing to
the government’s ‘ban’ on patenting the outcome of research based on public funding (in drastic
contrast with the Bayh–Dole Act in the United States in 1980). A Caltech team applied for similar technology in the same month as Fushimi’s patent was withdrawn (Kishi, 2004: 46–53).
In their original intention, ‘funneling’ is for describing rhetorical devices in the scientific text
to direct the readers’ concern from an abstract background to a specific issue. I adopt this termfor describing the selection process from early expectations to its targeted policy agenda.
In the pre-war period, Institute of Physical and Chemical Research (RIKEN) thrived as a large
financial conglomerate (zaibatsu), combining both basic and applied research. It engaged in
activities from building accelerators to selling products such as ‘RIKEN Vitamin’ (A) andsynthetic sake (Miyata 1983). After the Second World War, RIKEN was dissolved by theGeneral Headquarters, surviving through that difficult time as a limited company KAKEN(acronym for the Institute of Science) from 1948 to 1958 (RIKEN, 2005).
Mutsu was constructed in 1968, but experienced minor nuclear leakage in 1974. The experiment was finalized in 1993. http://www.jaea.go.jp/04/aomori/nuclear-power-ship/index.html(accessed 13 May 2012).
Wada may be seen as an example of a ‘big man’ (Sleeboom-Faulkner and Patra, 2011); asHayashi (2006) discusses in the case of Japan’s genomic policy, however, this can be also interpreted as a lack of ‘boundary organizations’ (Guston, 2000) in Japan’s landscape of science
policy, necessitating that people like Wada fill the gap with his personal network.
Gelfert (2012) analyzes a similar exchange between Japan and the United States at the launchof the National Nanotechnology Initiative (NNI).
The eight hubs were covering major national universities and institutions: the Universitiesof Tokyo, Osaka, Kyoto, Hokkaido, and Yokomaha City as well as KEK (High Energy
Accelerator Research Organizations) accelerator laboratory.
In some university laboratories, an escape route was invented by counting as plural the intermediate shapes of the folds within the same protein to attain the target (Interview 2). Masuda(2002) had already warned of this possibility.
Some of those who participated in the Human Genome Project (HGP) also raised their voices
against the monopoly of funding by protein researchers, arguing that genomics still needed to
be funded (Shimizu, 2000).

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Author biography
Masato Fukushima is a professor of social anthropology and science and technology studies at the
University of Tokyo. His academic interests lie in laboratory studies, post-genomic life sciences, thenano-bio interface, and computational infrastructure. Articles include ‘Between the laboratory andthe policy process’ and ‘Blade Runner and memory devices’ in EASTS, ‘Corpus Mysticum Digitale’in Mortality, ‘Resilience in scientific research’ in Science as Culture, and ‘Value oscillation in
knowledge infrastructure’ in Science and Technology Studies, some forthcoming.

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