The Role of the State and the AJS

The prominent role of state governance in science, education and industry speaks for itself in Japan, known for its ‘iron triangle’ between government, bureaucrats and heavy industry (Johnson Reference Johnson1982). Since the introduction of the Japanese version of the Bayh-Dole Act in 1999, and the independence of Japanese universities in 2004 (Takenaka Reference Takenaka2005), academia is encouraged to forge collaborations with industry. Nevertheless, until the introduction of the PDA Act in 2014, it had been difficult to tempt heavy industry to invest in medical innovation (Umemura Reference Umemura2011). In the context of the US, however, Mirowski and Sent (Reference Mirowski, Sent, Mirowski and Sent2002) regard a clear separation between ‘pure’ science supported by the state and ‘applied’ science as supported by industry as an untenable ideology, rejecting the notion of scientists as self-interested and science as market-driven (Mirowski and Sent Reference Mirowski, Sent, Mirowski and Sent2002: 15, 23). But in the context of Japan, as we shall see, not taking into account this distinction would be unrealistic, as Japanese scientists observe major differences between ‘pure’ and ‘applied’ science and ‘state’- and ‘industry’-supported research settings. Although these separation-lines may seem artificial and subjective, the distinctions form an important point of orientation for scientists and policy-makers with very real social and financial consequences for the way science is organised and practiced. It is this distinction that allowed the Japanese state to guide the science markets according to its own redemptive vision: the AJS.

The AJS was first formulated as part of the Health and Pharmaceutical Promotion Strategy and the five-year Medical Innovation Programme (MEXT 2012), which were to address the problems of ageing society and economic slow-down through regulatory reforms and make firm industrial and political commitments in support of regenerative medicine. Apart from turning Japan into the world leader of pluripotency, the AJS would be relied upon to boost the export of new medical products and devices to the Asian market (Headquarters for Healthcare Policy 2014) The All Japan System (オールジャパン体制) envisaged ‘a system for All-Japan collaboration and co-ordination’ and refers to the collective efforts to set up a structure for the advancement of a system for iPSC research (JTS 2008) supported by MEXT and the Stem Cell and Regenerative Medicine Strategy Working Group. Former Cabinet Secretariat Toshihiko Hoshino, professor and assistant director of the Basic Technology Research Division (MEXT), was tasked with building an all-Japan promotion system in collaboration with related ministries and agencies and industry to support regenerative medicine using iPSCs originating in Japan (CiRA 2012).

The AJS was to form a bridge between basic research in academia and industry to create new applications coordinated through national centres and universities; and it centred on Shinya Yamanaka’s work on iPSCs. The AJS was led by Kyoto’s Centre for iPS-cell Research and Application (CiRA), headed by Yamanaka, who was made responsible for the improvement of iPSC lines and culture technologies, including assays. The AJS network was built on four All-Japan pillars of iPSC research, involving Kyoto University, represented by Shinya Yamanaka (CiRA), who was to oversee the creation of technologies for the development of safe and efficient iPSCs, the development of iPSC proliferation control and for the evaluation of clinical response; RIKEN, represented by Yoshiki Sasai, responsible for developing technologies for cultivating and determining the efficacy of multipotent stem cells, including iPSCs; Keio University, represented by Hideyuki Okano, responsible for developing iPSC treatment with a focus on the central nervous system; and, Tokyo University, represented by Hiro Nakauchi, responsible for developing iPSC lines and treatment centered on blood cells (see Figure 6.1). Importantly, AJS made CiRA central to the distribution of iPSC lines, intellectual property and the handling of research results, and it stipulated that the tentative regulation of the research network of AJS was based on common rules. These policies, as we shall see below, restructured the science both organisationally and substantively.

Figure 6.1 MEXT’s promotion system for iPSC research toward building an All-Japan system.

Courtesy from the Japan Science and Technology Agency, reference material, https://www.jst.go.jp/keytech/h20-1sanko.pdf (22/1/2024).

In the following extract from a CiRA Newsletter (CiRA 2012), Professor Toshihiko Hoshino describes the AJS as the redemptive force behind the regulatory overhaul:

A collective effort would mobilise resources in support of the long-term vision of iPSC cures.

The realisation of the AJS vision required overcoming institutional barriers to research promotion:

This plan made CiRA central to the iPS promotion strategy requiring other institutes to adjust, including scientific and ministerial ones, so as to realise the promise of iPSC research to society. Down-regulation was key to the realisation of AJS.

The re-brokering of Japan’s regulation radically affected regulatory developments internationally (see Chapter 8); but in this chapter, I focus how the regulatory reforms inspired by AJS affected Japan’s iPSC research community.

AJS and Collaboration

Scientists’ competing interpretations of AJS provide nuance to dominant views of the regulatory reforms and show how AJS was designed to misread what was actually going on. My conversations with scientists on All Japan collaboration at CiRA, iCeMS and CDB illustrate this. Takayama, an administrator from CiRA, Kyoto University, gave his view of AJS:

CiRA, an independent research institute, was one of the main beneficiaries of the life-science policy’s focus on iPSCs and regenerative medicine. It is supported by the Japan Science and Technology Agency (JST), which funds science and technology targets created by the Japanese government (JST 2021) and is a main financial backer of the AJS. Kawa, a researcher at iCeMS, Kyoto University, had a different view. ICeMS is supported by the World Premier International Research Centre Initiative (WPI), which was launched in 2007 by MEXT in a drive to build within Japan ‘globally visible research centres that boast a high research standard and an outstanding research environment’ (WPI 2020). Kawa said:

Kawa did not think that the AJS prioritised patients. He also emphasised the national focus of AJS. But the official version of the Health and Pharmaceutical Promotion Strategy had also announced collaboration with other Asian countries. Therefore, I asked about possible collaboration. Kawa said:

In Kawa’s interpretation of the Health and Pharmaceutical Promotion Strategy, Japan is hoping to export regenerative medicine products, while CiRA’s iPSC activities develop them in Japan. As scientists frequently pointed out, at CiRA one in thirty PIs was not Japanese (‘only one foreigner’), while iCeMS was required by its funder, WPI, to have 30 per cent foreign staff. But then, international collaboration is part of WPI’s mission statement. Asking about CiRA’s working relations with other institutions, such as the Medical School, Kawa responded:

As repeatedly confirmed, the Medical School regretted the concentration of funding on iPSC research and CiRA. The Medical School wanted the funding to go to more urgent research, judging it too early for clinical applications using iPSCs. In 2013, these diverging views made collaboration difficult. According to an experienced legal scholar from Kyoto, Abe, the Japan Medical Association was also reluctant to support clinical applications using iPSCs:

The term ‘regenerative therapy’ gained currency, including in government documents. The term, in his view, reflects anxiety about the clinical application using iPSCs – not just about whether it will work but also about its safety, even in the case of RPE, which is supposed to be relatively safe, due to the low number of iPS-RPE cells involved and their traceability in case the eye socket is pierced. Nevertheless, being the first in-human study, there was much apprehension about Takahashi Masayo’s iPS-RPE application.

The views above all pinpoint practices that have been mis-recognised by the AJS. First, the national focus on iPSC research as an all-Japanese iPSC production-line loses out of sight the plight of its poster-patients. Second, rather than a united effort of Japan’s best scientists, iPSC researchers were privileged by the JST and AMED. Third, rather than the collaboration with Asian countries, the AJS-policy strategised to export therapy products to lift itself out of its long-term economic slump. Fourth, rather than unity among iPS experts, many preferred independence, and some paved their own way to collaborate with overseas researchers. In addition, the will to successfully innovate was translated into regulation that presumed a form of therapeutic efficacy not recognised by the medical community. In other words, critical observers recognised the AJS’s misrecognition of what was going on in practice.

Friction in the Coordination of iPSC Research

Apart from misreading its collaborative dimension, AJS misread the smoothness of iPSC research coordination and the workload of scientists. As illustrated below, although the AJS enabled iPSC research through regulation and funding, the very coordinative functions assigned to CiRA also had disabling effects. For instance, the AJS encouraged the use and development of ‘Japanese’ standards through CiRA’s leadership. Most work on iPSCs involved collaboration with CiRA, and requesting iPSC-lines from its stock entailed the use of CiRA’s standards and methods, because ‘CiRA takes responsibility for the genome analysis involved and the user research centre for the tumorogenicity studies’ (Azuma and Yamanaka Reference Azuma and Yamanaka2016: 37). Thus, if a research centre derives iPSCs from sources other than CiRA for therapeutic use, the centre in question and CiRA would also have to characterise and analyse the differentiated cells together. Established researchers expressed frustration with the dependence involved in this ‘collaborative’ arrangement.

The examples that follow concern the research practice around the first clinical iPSC application in humans with AMD and the centrality of CIRA’s strategy regarding the global standardisation of its methods. The clinical application took place at RIKEN-CDB, Porto Island, in Kobe, in collaboration with the Foundation for Biomedical Research and Innovation (FBRI) – next door – and CiRA at Kyoto University. Masayo Takahashi, the PI of this clinical application of iPS-RPE, had moved from the University of Kyoto, as she found its Medical School’s ‘conservative attitude’ to iPSC applications disagreeable. According to a researcher on the project, she was happy about the regulatory reforms that had been formally announced:

A great step forward, the researcher explained, is that the RM Act facilitates the outsourcing of cell processing:

Using a company seems to take pressure away from the PI. But as collaboration with a company introduces new possibilities, other pressures appear, as we shall see below. Of immediate importance to the pilot study was the availability of a Cell Processing Centre (CPC) at IBRI. Collaborating with CiRA, Takahashi uses Yamanaka’s assays to test the autologous (from the patient) iPSC–derived neuron stem cells to generate RPE. A ‘scientific mediator’, who mediates between scientists on regulatory and coordinative issues, explains the centrality of CiRA in their work:

This collaboration was crucial to the AJS vision, as it was widely thought that the first successful iPSC applications would become a global standard. The same mediator explained:

In the context of AJS, the first successful in-human application of iPS would have had to make use of ‘the Yamanaka assay’. But the development of assays is part of a long-term process of trial and error and something that scientists find important to experiment with. Without having a say in the use of assays, Kimura, a decision-maker in FBRI, where the clinical application takes place, commented that FBRI could not be held accountable for the iPS pilot-study (Kimura, 7/11/2013*). The translational researcher in charge, Hashigawa, further clarified this stance in relation to how CiRA frequently changed protocols:

This researcher summarised the AJS as ‘A bad idea, promoted by the bureaucracy’. ‘The power of Yamanaka and Takahashi’, in his view, ‘should be limited to their own field’, that is, basic research. This researcher was clearly upset about ‘having to use Yamanaka assays and feeders [when testing patients], just because these have to become world standard’ (Hashigawa 1/11/2013*).

The symbolic violence with which the AJS created a Yamanaka-discourse and a Yamanaka personality-cult in the media also seemed to transcend the wish of Yamanaka himself. In fact, Yamanaka had tried to resist the media-rituals and bureaucracy that had turned him into ‘Mr iPS’. Hiroshima, a vice-president of Academia Japan, the company that licenses and brands CiRA/Yamanaka products, explained that it is the mission of Academia Japan to advertise and turn Japanese iPS into a global success. The wide use of ‘Yamanaka assays’, ‘Yamanaka cell lines’ and ‘Yamanaka methods’, he related, was crucial to the company. Hiroshima laments:

These comments illustrate some of the frustrations generated by the conflicting demands of scientists and managers under the political requirements of the AJS.

The AJS spirit behind the regulatory reforms had been able to facilitate iPSC research applications but not without creating frictions through the coordination requirements that are part of its All-Japan vision. International collaboration is to serve All-Japan, while All-Japan coordination means a hierarchic leadership headed by CiRA. AJS caused frustration: Academia Japan found marketing ‘Yamanaka’ brands hard; scientists disliked having to use assays just because they are to be patented by Academia Japan; medical institutions did not want to take responsibility for applying assays; and, the world was not waiting for Yamanaka iPSC lines and assays.

Scientists’ Options and Considerations When Planning Clinical Applications

As well as being framed by the AJS, the regulatory reforms were aimed at encouraging the commercialisation of regenerative medicine through the industry pathway for clinical trials using iPS and methods from the CiRA. The iPSC bank at CiRA provides cell-lines for industrial research (in accord with Good Gene, Cell and Tissue Practice, GCTP) and company sponsored clinical trials (PMDA 2021). Even though some researchers prefer doing clinical research using their own processed cells through the RM Act first, the research pathway, the AJS vision favoured working on clinical trials with the financial backing of companies through the industrial, PMD pathway, oriented to the marketing of regenerative therapies. The RM Act regulates the use in research or in medical procedures of unapproved regenerative medicine products in medical institutions. It has lower integrity standards compared to those of the PMD Act pathway. For instance, clinical research does not require GLP – only GMP-like conditions – and resultant data do not count towards clinical trial approval under the PMD Act (Azuma Reference Azuma2015). The RM Act pathway is also considered cheaper, though this may depend on MoHWL requirements for a particular application (Azuma Reference Azuma2015; Azuma and Yamanaka Reference Azuma and Yamanaka2016). The examples below illustrate how the introduction of regulatory measures supported by the AJS has shifted conditions for conducting clinical trials in such a way that they encourage making use of CiRA’s iPSC bank, collaboration with industry and an orientation on marketing rather than on scientific research.

Constraints on the Conventions of the Science Community

Research leaders in main iPS-hubs, though aware of its benefits, expressed doubt that the vision of AJS was conducive to conducting basic science; they were acutely aware of rebellion against CiRA’s central role in iPSC research and its standard-setting role. In particular, there was anxiety about the expected commercialisation of regenerative medicine and its distraction from basic science. Although working with industry may provide the funding and conditions for marketing to scientists working on regenerative therapies, such collaborations play havoc with ‘traditional’ modes of scientific research among academic colleagues.

The intense negotiations and skills involved in the acquisition of resources, the application for funding, permissions and certificates, maintaining relations with CiRA and accommodating the visits of audits and collaboration with hospitals take up much of a PI’s time and can be nerve-wracking. Many iPS scientists prefer to leave such pressures to company CEOs if they can. Nevertheless, being tied to a company places constraints on the conventional activities of the scientific community. One scientist involved in an iPSC application, Kishi, explains:

Collaboration with companies encourages secrecy and hampers scientific exchanges. When I met scientist Sumida, who uses iPS reprogramming to create cardiomyocytes at Keio University, I asked him why he did not collaborate with another scientist, who engaged in very similar research. He said:

This scientist does not use CiRA’s iPC reprogramming methods, both because he is tied to a patent used by the company he works with but also because in his view his vectors are better:

As such integration could lead to tumourisation, Fukuda does not see any reason to give up the Sendai vector. In fact, he prides himself of spending only twenty-five days on reprogramming and differentiation – ‘much faster than other methods’. When asked, Fukuda said he would also use the Sendai vector for clinical applications. But others who work with CiRA, such as Yanagishi from an Osaka-based research group that used CiRA iPSC lines to differentiate into cardiomyocytes, claim that the episomal plasmid is much better (Yanagishi, 3/12/2013*).

A number of researchers have experienced ‘suffocating influence’ through the AJS. Kishi aims to use iPS reprogramming to generate HLA- (human leukocyte antigens) and HPA- (human platelet antigens) controlled platelets for allogeneic transfusion. Kishi was diversifying his regulatory pathways for strategic reasons. He had begun preparations for a pilot-study at CiRA:

Kishi planned to make platelets using his own assays: ‘You do not need to test for gen- mutations: we can use irradiation to eradicate any contamination.’ This allowed him to work relatively independently. So, Kishi was going to use three different protocols for cell processing: one for a clinical pilot-study with KUH to produce platelets in the laboratory under GMP-like conditions, one for the generation of iPSCs with a specific HLA of GMP-grade cells for clinical investigation following the RM Act and one for large-scale production of GMP-grade platelets for industrial use with Megacaryon and Toray using the PDA Act. The combination of managerial and scientific work involved Kishi found taxing:

Apart from experiencing organisational difficulties, Kishi was also frustrated with AJS for what he regarded as ethical reasons: ‘Despite the low level of blood donation in Japan, Japan does not support the production of platelets: they believe that it is a social problem.’ Thinking that the US does not have these issues, Kishi was wondering whether to go for clinical trials in Japan or in the US. Europe was not an option, he reflected: it has good systems for blood donation.

The AJS-vision introduced new constraints and dilemmas in the work of scientists. First, scientists were pitted against one another insofar as they are encouraged to work with companies: competition between companies hampers scientific exchanges on research methods and academic collaboration. Second, the pressure to work with CiRA created dilemmas: some scientists used their own vectors for reprogramming, because they worked in their research or because they had commercial contracts that require their use. Third, scientists missed chances to experiment with assays and to develop their own theories about suitable standards. And fourth, increased competition and pressure to commercialise has pushed scientists to adjust their research designs and to collaborate with industry. In short, researchers’ attention to patient needs and scientific quality had shifted towards regulatory options and marketing.

Working with and around AJS Politics

The financial resources, responsibility and authority that came with research funding made CiRA vulnerable to critique and conflict about funding, priorities and methods. New modes of working affected the science itself.

Researchers have moved away from CiRA to other institutes for various reasons as a direct or indirect result of the implementation of the AJS-vision. Some objected to the hierarchic organisational structure at CiRA, rejecting political interference. Immunologist Shirai, who moved to Kobe, wanted to collaborate internationally in iPSC applications to counteract forms of cancer. Shirai explained why he left CiRA:

The ISCBI aims at the global harmonisation of quality control, safety and efficacy of human pluripotent stem cell banks and their derivative cell therapy products. Shirai believed that CiRA was only interested in setting Japan’s standards for the world to follow. His new institutional environment, by contrast, encouraged participation in this international initiative as it favours ‘real’ international collaboration.

Many researchers are disturbed by the focus on iPSC translation. For instance, one researcher of autologous iPS-derived MSCs for muscular skeletal conditions in, for instance, multiple sclerosis and rheumatism, concluded that the method does not offer prospects to patients over the age of thirty-eight. For this reason, he moved to another research centre to concentrate on physical rehabilitation. This, he believed, would be crucial to the success of any cell therapy for muscular skeletal disorders (Hameda 28/3/2013*). Other researchers, such as Nakatsuji Norio, openly argued that a focus on iPS drug-screening is the most viable use of iPS methods, but he preferred to use less costly methods from biochemistry to emulate cell functions using biomaterials and tissue engineering (Nakatsuji Reference Nakatstuji2015: 101). Tissue engineers, such as Tanida from IFMS, felt they were passed by unwisely: ‘You need scaffolds to get the cells to work.’ Tanida had developed a sponge to deliver growth factors to the affected tissue. Like other leading tissue engineers, such as Okano and Iwata from Tokyo, Tanida said, tissue engineers have lost out to medical professionals that translate iPSC research too early:

Tanida decided to work on iPSCs to get funding that would also support his research. But he felt uncomfortable doing so, as his main expertise is making the cells work through scaffolds. He explained that ‘assays and vectors are predetermined’, criticising government policies and the Forum for Innovative Regenerative Medicine (FIRM) for mainly investing in large companies that will take the industry abroad to make profit. Other researchers echo this critique. Although Tanida supported a policy that encourages collaboration with industry, the AJS neglects small specialised companies even though ‘you need them for ideas to create devices useful for both the lab and the science’ (Tanida, 15/11/2013*).

Some researchers criticised AJS for the practical consequences of its emphasis on using the same vectors and assays, while others were more worried about scientific classifications of pluripotency and international banking standards. Cell biologists pointed out that science is universal and requires universal standards for measuring pluritpotency across the fields of hESCs and iPSCs (see also Nishikawa, Goldstein and Nierras Reference Nishikawa, Goldstein and Nierras2008). Fierce supporters of this stance were leading researchers of hESCs. One expert lamented the ethical halo of iPSC research:

Until iPSC research became the focus of attention, hESC-research had slumped, due to strict regulation and ethical issues of oocyte donation (Slingby et al. Reference Slingby, Nagao and Akabayashi2004). A leader in hESC-research and regulation commented that policy-makers decided rather late that encouraging hESC-research would support the iPS venture (Umeda, 27/2/2016*). Another leader of hESC-research criticised CiRA’s iPSC bank as a waste of money and efforts, because allogeneic applications still require immune suppressants. Instead, he recommended emulating Pfizer’s example:

Many scientists were in favour of conducting hESC research but did not think Japan’s regulatory climate made it viable.

Another reason for opposing AJS related to the need for international industrial standards for production. Hashigawa, from Kobe’s FBRI, did not just work on clinical applications of iPS research but also on those of MSCs, T-cells and gene therapy. He worked in both laboratory and clinic and acted as business consultant on international standardisation. Hashigawa said that he could not find international collaborative partners in Japan due to the national focus of the AJS. This is why Hashigawa and his team had started to work on new industrial standards in the context of the International Alliance for Biological Standardization (IABS) (cf. Abbot et al. Reference Abbot, Agbanyo, Ahlfors, Baghbaderani and Bartido2018) and the ISCBI. He compared it to ICH-guidelines for good clinical practice in the pharmaceutical industry, providing guidelines for GMP and risk-management in regenerative medicine:

In the meantime, PMDA leaders had also realised that the internationalisation of regenerative therapy necessitates the creation of such a system. But there are researchers who object to the hijacking of Japanese science through companies that move abroad. One research-leader, for instance, fiercely opposed the collaboration of Takahashi Masayo with Healios, believing its establishment of a branch in the US was an omen of selling out iPS to the US (Yamaguchi, 14/11/2013*). Other researchers, however, claimed that a nationalist emphasis on the Japaneseness of iPS had set the scene for the scandal around STAP (Stimulus-triggered acquisition of pluripotency)-cells at RIKEN-CDB (Tsuji, 05/2/2016*; Takehara, 26/2/2016*), which involved the attempt to create pluripotent stem cells by applying stress to ordinary cells (Cyranoski Reference Cyranoski2014). For a few weeks, STAP-cells shook the world, as it was thought that they were even easier and quicker to produce than iPSCs (Suda Reference Suda2015). Its dismantling left RIKEN-CDB considerably weakened (Normile Reference Normile2015). In fact, the STAP scandal resulted in the closure of the CDB (Osaka, 27/1/2016*) and its and reassignment of many of its former labs into a new institute, the Centre for Biosystems Dynamics Research.

The AJS has made iPSC research central to Japan’s quest for ‘regenerative therapies’. Funding and infrastructure support emphasised iPS over other branches of science such as tissue engineering and hESR. AJS’ encouragement of collaboration with industry took resources away from basic research and hampered collaboration with small specialised companies. Many researchers used the AJS-vision as an opportunity, but others viewed it as a hindrance. Of the latter, many grudgingly adjusted their research focus and methods, but others moved to different fields. There was conflict especially around the focus on Japan. Some researchers advocated for CiRA’s international leading role, while others emphasised the importance of more fundamental collaboration in industrial and scientific standard setting, while again others criticised AJS for making iPSC research vulnerable to profiteering companies that go abroad.

Bringing Health Organisations Together to Discuss Needs, Challenges and Governance

On 18 and 19 May 2015, my colleagues and I convened an international network workshop in Brighton for HOs, UK.Footnote ¹ Apart from being an opportunity to network with international HOs, the meeting aimed to identify factors HOs consider when setting priorities in addressing their challenges and needs. As it seems obvious that HOs for different conditions have different needs and challenges, a conversation among the representatives of HOs for conditions such as spinal cord injury (SCI) and muscular dystrophy (MD) from various parts of the world seemed useful for consideration of internationalising particular activities. SCI involves damage to any part of the spinal cord or nerves at the end of the spinal canal – often causing permanent changes in strength, sensation and other body functions below the site of the injury. MD, of which there are many types and subtypes, is a hereditary condition marked by progressive weakening and wasting of the muscles. Delegates from five patient organisations for SCI (South Korea, India, Europe, US, Japan) and six for MD (China, Taiwan, India, Europe) participated in the meeting.

A focus on the conditions of MD and SCI is relevant to the question of the needs of patients and their HOs and how to address them. First, MD and SCI are often mentioned in the scientific literature as urgently requiring biotechnological solutions (Sohn and Gussoni Reference Sohn and Gussoni2004; American Academy of Orthopedic Surgeons 2016). In HICs in particular, significant government funding and scientific efforts are invested into finding a ‘cure’ for these serious and intractable conditions. Second, individuals with MD and SCI have diverging disease histories and treatment, which are likely to affect the aims and activities of HOs. And, third, former research indicates that people with MD in Japan are much less preoccupied with regenerative medicine compared to individuals with SCI and that persons in different parts of the world to a different extent look to science, the state, alternative therapies and society for different ways of managing disability (Kato and Sleeboom-Faulkner Reference Kato and Sleeboom-Faulkner2018).

At the meeting, HOs discussed their main challenges, the governance of their organisations, treatment and research needs and experiences with collaboration with industry and knowledge activism. In break-out groups and plenary sessions, discussions were held both among delegates with the same medical condition from different regions, and among delegates with different medical conditions from the same region. Discussions were recorded, transcribed and analysed in terms of the thematic contents of priorities, the pros and cons of working with industry and the importance attached to scientific innovation and regulatory facilitation. Although delegates emphasised the global nature of problems related to SCI and MD, discussions were usually self-framed in terms of wealthy (HICs) and poor (LMIC) and Asian and Western forms of governance. Significant examples (Timmermans and Tavory Reference Timmermans and Tavory2012) related to the question of how to address needs and challenges were used for this chapter.

During the workshop, ‘patient organisations’ defined themselves variously as patient organisations, halfway houses, projects, associations, foundations, alliances and networks. Referring to them collectively as ‘health organisations’ (HOs) seems appropriate, as they share a focus on activities aimed at supporting, maintaining and improving health conditions. Not all members of HOs can be considered ‘patients’ (also see Rabeharisoa Reference Rabeharisoa2006), in the sense of being under treatment by a medical institution. Even persons who live with serious conditions, such as SCI and MD, often do not self-identify as patients (Kato and Sleeboom-Faulkner Reference Kato and Sleeboom-Faulkner2018), while family, friends and professionals can also be members of HOs and sometimes even dominate them (also see Landzelius Reference Landzelius2006).

The sections below explore whether the wish for down-regulation in the interest of patient movements is universal. The first section asks what HOs view as their main challenges and how they relate to political governance; the second explores the needs of members of HOs per condition and per location and their preferences for treatment and research; the third reflects on collaboration with industry and knowledge activism. The conclusion of this chapter considers the implication of the redemptive ideology of FTCM and down-regulation for DM and SCI in an international context.

Locally Situated Needs

When describing the needs of individuals with MD and SCI, HO delegates made clear that they vary per country, especially regarding disposable income, government support in terms of income, policies of equality and public provisions regard traffic, transport, education and healthcare.

Income support for persons with disabilities in China and India is paltry compared with that in Japan, South Korea, Europe and the US. An Indian delegate expressed this as follows:

According to another delegate from India, some 60 per cent of the government aid for individuals goes to intermediaries, ranging from bureaucrats to bribes for the postman. Delegates emphasised that in rural India and China disability registration is important to get access to income support. Without awareness of the need to register, many families do not receive financial support and struggle to look after the ‘disabled’.

An issue emphasised by delegates from India and China but common to all HOs for SCI was the public provisions necessary for wheelchair users, including traffic regulation and accessibility. Its importance lies both in the enhancement of the quality of life and the prevention of SCI. An increase in traffic safety and safety equipment and the aging of society influence the SCI demography. A delegate from the UK explained:

Apart from requesting measures for traffic safety, HOs for SCI from LMICs emphasised the urgency of education for SCI persons to gain employment and the need to combat discrimination on the basis of disability and gender. Though HOs in other societies face similar issues, they were not considered as important. HOs in HICs focused on issues of legal representation, which privilege the rich and emphasised the need for scientific research.

The diverse social and financial concerns of HOs for MD in different locations pertained especially to medical needs, diagnostic services and social status. HOs in HICs emphasise the need for public awareness, facilities in schools and scientific research. By contrast, MD delegates from India and China pointed to the need for more resources for genetic testing and for more expertise and funding for training volunteers with medical proficiency. While Indian and Chinese MD HOs brought up the shortage of rehabilitation centres, they emphasised the availability of Ayurveda and Traditional Chinese Medicine alongside the use of steroids and other medicine for pain management.

As for social status, it was emphasised that in India women are generally expected to look after the disabled. The MD carrier status of women often leads to mothers being blamed and subsequently to divorce and children being relocated to orphanages (Thomas et al. Reference Thomas, Rajaram and Nalinia2014). A Chinese delegate echoed that mothers are victimised and often blame themselves for their child’s condition. But although some parents end up divorced, other couples deal with the condition as a family (Sui and Sleeboom-Faulkner Reference Sui and Sleeboom-Faulkner2010). Japanese research reveals that the birth of a child with MD can easily escalate into a conflict between the families of the parents, though this may have comparatively less severe financial consequences (Kato and Sleeboom-Faulkner Reference Kato and Sleeboom-Faulkner2018). These gender and family issues greatly impact the kind of care and medical needs HOs must cater for.

Table 7.1 summarises the most urgent needs indicated by the delegates of people with SCI and MD in LMICs and HICs. There is a difference in emphasis, whereby LMICs needs for income support, education, diagnostic facilities and rehabilitation centres seem to be more basic than in HICs, where scientific research, legal representation and support for the elderly (SCI) are emphasised. As was pointed out by several delegates, HOs in HICs often assume the availability of basic healthcare to HOs in LMICs. In addition, the role of the extended family in care, severe social stigma associated with disability and the everyday use of alternative medicine rank lower on the agendas of HOs in HICs. This variation in needs and conditions makes for great differences in HO workspaces.

Locally Situated Demands for Treatment and Research

HOs for SCI and MD desire and support scientific research, but their priorities and reasons for pursuing treatment and scientific research differ. All delegates from HOs for SCI hoped for science-based cures, including regenerative medicine, exon skipping – a therapy option for Duchenne MD (Dzierlega and Yokota Reference Dzierlega and Yokota2020) – and robotic applications. There was some agreement among Western HOs that the pursuit of evidence-based medical cures has its drawbacks. An American delegate explained that, in 2015, there were over 700 clinical trials, but clarity about their quality was lacking. Stem cell trials were not an option for her:

An SCI organisation from the UK had also become cynical about the timescale:

Persons with SCI in HICs weigh their choices:

With fewer health and educational facilities, patients in LMICs that can afford to do so pay for medical interventions at stem cell clinics, such as Beike Biotech and the Xishan Institute in China and Neurogen and New World in India (Song Reference Song2011; Bharadwaj Reference Bharadwaj2013; Sleeboom-Faulkner Reference Sleeboom-Faulkner2016). Although delegates indicated a lack of reliable information, the use of the internet and WeChat (weixin) facilitates the exchange of experiences and tips about the reliability of experimental medicine.

Clinical trials for SCI – such as those conducted by the Spinal Cord Injury Network (SCIN) – have moved from the West to China and India. The Indian delegate doubted that the Network would have gone to India, had it been successful in recruiting patients in the US. In this delegate’s view, the threshold to participate in clinical trials in LMICs is lower, due to a lack of access to reliable information sources and suitable healthcare and employment options. Primary motives for participation are improved bowel- and bladder-management and regaining the ability to walk. But the delegate’s organisation currently does not recommend any therapies.

HOs for SCI in South Korea and Japan are informed about new treatments through these scientific contacts at home and HOs abroad. In Japan, homegrown therapies, such as iPSC and stem cell–based clinical interventions, exon-skipping and Hybrid Assistive Limb (HAL®) (Walk Again 2015), have gained much attention. To gauge the reliability of clinical trials the Japanese association for SCI usually looks to the government for advice:

In contrast with other delegates, a Japanese delegate emphasised the trust invested in the Japanese state:

The South Korean delegate explained that his organisation, which used to strongly support a well-known, but maligned, stem cell scientist, Hwang Woo-suk, now distrusts scientific promises:

There was agreement among delegates that most people with SCI in HICs focus on rehabilitation, which is also gradually becoming available in LMICs. Discussion ensued on the SCI patients’ duty to do physical exercise. A US organisation considered it as a responsible step towards clinical trial participation:

The responsibility to remain healthy before participating in a (usually free) clinical trial contrasts with situations in less wealthy areas, where no rehabilitation is available in areas with little wheelchair access and few employment opportunities.

All delegates had closely observed patients go for experimental treatment – with Indian HOs actually arranging for patients to do so. The exception was the Chinese organisation for MD, which only recommended standard medicines: ‘If patients want anything else, they need to find it and pay for it themselves’ (Li, 18–19/5/2015*). HOs in HICs are usually only prepared to provide information but try to record the experiences of patients that decide to undergo experimental clinical interventions. Most HOs object to commercial charges for experimental medicine and criticise it as ‘medical tourism’. HOs for MD in HICs have researched ‘therapies’ advertised in Asia. Delegates emphasised that MD organisations in HICs now avidly follow developments in exon-skipping, gene therapy and iPSC applications. In most countries, HOs for MD support scientific research with data from patients. In some cases, the state mediates these efforts. For instance, in Japan, the Japan Muscular Dystrophy Association (JMDA) is a member of the national MD-research collective called Remudy (Remudy 2021), organised and sponsored by the Ministry of Health Welfare and Labour.

Although all delegates supported the search for treatment and scientific research, it is clear that the cultural politics of countries make for different workspaces. HIC’s HOs for SCI emphasised the need for scientific medical cures. They usually advise against experimental treatment and are sceptical of the ability of clinical trials to deliver miracle cures. Nevertheless, they valued collaboration with industry and emphasise individual responsibility for body maintenance through self-discipline and exercise. In Japan, China and South Korea, delegates emphasised the importance of the state in the search for therapy. In Japan and China, HOs follow government advice about therapies, while in South Korea, faith in state-supported stem cell therapy was lost after the Hwang scandal. MD-HOs attach importance to research and therapies that can ameliorate the condition. Here we see that most HOs advise against commercial treatment claiming to provide cures and encourage long-term collaborations with industry, although some HOs in the past have tried to mediate such treatments.

Collaboration with Industry

Collaboration with industry can mean a chance to acquire expert medical advice on treatments, especially important for LMICs, and to access up-to-date information about the availability and costs of new medicines, technologies and interventions. It is also an opportunity to put priorities on the research agenda and ensure that the research concerns translational research, aimed at the market. A successful collaboration with industry can mean gaining credibility as a HO. But as we shall see, HOs in LMICs have less leverage to negotiate compared to HOs in HICs.

Collaboration can entail risks. Mentioned as most worrying were the lack of scientific transparency, not having control over goal-setting and the abuse of trust. All HOs worried about ‘getting into bed with the devil’, as expressed by a UK delegate (Brown, 18–19/5/2015*), that is, collaborating with ‘rogue’ companies. One HO from India raised the example of a pharmaceutical company that offered patients a weekly sum of £250 for providing a blood sample, including clinical and other data, without revealing its exact purpose. HOs also fear losing the ability to steer research priorities if they accept funding. Sometimes researchers use patients to find answers to theoretical issues, ignoring the therapy-oriented agenda of HOs. Coca-Cola, for example, would have funded an exercise programme for the ‘disabled’, mainly to improve the company’s unhealthy image. Another anxiety is that some companies try to use patients to acquire insurance pay-outs for them. For example, a delegate related how one exoskeleton company tried to pressurise SCI HOs to persuade GPs to prescribe expensive suits of approximately £100k.

To diminish the risky aspects of collaboration with industry, the British HO for MD advised the use of a strong Memorandum of Understanding (MOU): ‘It is important to stick to moral standards, as some companies prey on our vulnerability’ (O’Hara, 18–19/5/2015*). While the UK organisation recommended raising funds only after identifying clear targets, HOs in India and China emphasised the difficulty of attracting any funding. One Indian HO followed strategies to make themselves attractive as a business partner. For instance, they promised to introduce buyers to a wheelchair company in exchange for wheelchairs with particular specifications. A less successful example in India was the initiative to negotiate low fees for stem cell ‘treatment’ in exchange for patient introductions (Basu Reference Basu2012). The therapy was not successful, and the HO did not have the resources nor the expertise to sue them. HOs from Europe recommended the involvement of regulators that are open to lay-expert input in clinical trials. For example, the ‘unscientific’ end-points, such as ‘the ability of a boy to scratch his own leg’ (Brown, 18–19/5/2015*) have substituted the formerly standard six-minute walk test, which was of little relevance. In Italy, involvement in clinical trials enables the MD community to get useful feedback on psychological aspects and the placebo effect of clinical trials. This situation contrasts with HOs from China and India, which usually approach scientists individually or rely on symposia for information.

Some HOs in HICs are strong negotiators, as they can set their own targets by mediating between industry and scientists. An American HO brings together companies, government officials, clinicians and scientists at conferences and finances research, making sure that its priorities are supported:

A UK HO for MD was aware of the great value of conferences to pharmaceutical companies: ‘They pay anything to speak with patients face to face’ (O’Hara, 18–19/5/2015*). In Japan, similar conferences are held, but the government – an important research funder – plays a more important role as mediator, while in South Korea, the SCI HO has become weary of working with industry after the data-fabrication scandal (Resnik et al. Reference Resnik, Shamoo and Krimsky2006). Short on financial and state support, Indian HOs expressed vulnerability in negotiations with companies. For instance, initially free/cheap drugs can sometimes suddenly become expensive. Though this can also happen in HICs, poor insurance conditions make the drug markets in LMIC unattractive (WHO 2012). In other cases, however, a tiered payment system is used so that poor patients receive free treatment (Hayden Reference Hayden2014). An Indian HO considered the presence of a scientific advisory board and legal representation to be crucial for minimising risk in dealing with industry. The Chinese MD organisation, however, did not collaborate with companies, as ‘they are motivated by profit and can say anything’ (Li, 18–19/5/2015*), and would rather work with scientists in state institutions and the government.

HOs from HICS and LMIs generally shared perceptions of the risks and opportunities of collaboration with industry (see above and Table 7.2), but in their respective workspaces, delegates from HICs displayed more confidence in their ability to influence research agendas, while delegates from LMICs worried more about their credibility. In dealing with risks, the discourses of delegates from HICs were assertive and those from LMICs timid, conveying a sense of dependency: HIC delegates discussed ways of creating a ‘strong MOU’, sticking to moral standards, involving regulators and making demands of universities point to assertiveness, while LMIC delegates spoke in terms of becoming attractive to companies, aiming for long-term, reliable, collaborations and building relations of trust.

Knowledge Activism

Health or patient activism refers to health activities engaged in creating critical awareness and political, including regulatory, change. Knowledge activism, which emerged in Western HOs relatively recently, supports health activism. Traditionally, HOs engage in health activities that are not necessarily ‘activist’, as it was not directed at political change or addressing matters of social justice. For this reason, the global spread of ‘knowledge activism’ requires a rethink of issues of identity-making and of governance (Rabeharisao et al. Reference Rabeharisoa, Moreira and Akrich2014). A distinction between HOs activities and knowledge activism highlights difference between activities of HOs for HICs and LMICs and between HOs for different conditions.

The activities of HOs include education in schools, of families and the public through books, films and social media and the training of researchers and nurses. Most also have a newsletter, a website, instructions for emergency posts and a registry. In some countries, health activities are more ‘activist’ than in others. For instance, some HOs spoke of ‘liberating people living with SCI’, ‘spreading awareness’ and ‘empowering patients’, while others described their activities in terms of help, acceptance and sharing. The British SCI HO and the international HOs for MD and SCI work on international services to signpost research, clinical trials, IT and practical information, ranging from housing adaptations to bladder and bowel management. Some HOs in HICs engage in specialist education, such as training people in the newest computer technology, assistive technology training for volunteers, occupation therapists and managers so that new technology, such as for mouth control, can be used by many patients.

HOs in LMICs put much effort into activities related to basic needs. A delegate from an Indian SCI HO clarified that India needs accessible traffic and public provisions before it can begin to have a science focus. The HO liaises with government to set up rehab centres, provides wheelchairs and equipment for members and is in the process of compiling an accident and emergency (A&E) manual and a registry for its members. A delegate from a Chinese SCI HO described how they tried to persuade medical centres and the government to establish rehabilitation centres and how they raise money to train people with SCI to re-enter the labour market and to regain their self-respect.

Of the differences between HOs, those related to knowledge activities are most prominent. Knowledge activism concerns the creation and mobilisation of knowledge, including data-gathering activities related to treatment experiences, exchanges of narratives, medication, and medical data potentially usable in the creation of biomedical knowledge, health technology assessment, public health research and forms of judicial expertise.

In the US, HOs try to influence research policies by lobbying government. For instance, the US SCI HO supported a bill for research, The Dana and Christopher Reeves Act, and a freedom of choice bill for allowing therapy provision outside the FDA (Holbein et al. Reference Holbein, Berglund, Weatherwax, Gerber and Adamo2015). Apart from mediating and steering research, this HO demands that scientists replicate studies and persuades universities to waive overheads and match research funding. The British HO for SCI creates scientific reviews of research strategies, organising conferences and workshops for international lay- and expert audiences. The South Korean HO also organises annual conferences with US nurses, scientists and activists to shape the South Korean research agenda. The Japanese SCI HO, while providing information on clinical trials and health management, also emphasises the need for coordinating with scientists and HOs abroad. The organisation lobbies the government and scientists to develop regenerative medicine, robotics and new approaches to rehabilitation and organises conferences and public lectures to support research.

The delegates from MD HOs maintained that their HOs have all set up registries for various forms of MD. But their use differed per geographical location. In India, registries primarily serve as a tool for patients to enter clinical trials, in Europe, to integrate data for scientific research, and, in Japan, to synchronise drug-development with other countries (also see Kumamoto University 2011). The international MD HO engages in data collection for a registry for clinical trials in Europe, creates documents outlining the pros and cons of clinical trials, campaigns for the reimbursement of clinical trial participation costs and organises conferences, workshops and webinars for patients and researchers internationally.

All HOs engaged in social, informational, social media and educational activities (see Table 7.3), but only HOs in HICs provided training to adopt the newest biotech, and only HOs in non-Asian HICs engaged in international information services. The knowledge activism of HOs in HICs in national and international research activities attests to a much higher involvement with scientific research compared to HOs from resource-limited countries, where scientific activities were mentioned only in the form of participating in or being invited to scientific workshops. And it is this expectation to direct activities to global knowledge activism, which can aggravate dissonance between available resources and demands in the workspace of non-HIC HOs. For when it comes to local health needs, it is clear that for LMICs the priority lies with basic healthcare and policy measures (regarding road traffic, discrimination, education and registration), while in HICs education and funding for research/clinical trials are high on the list. Nevertheless, in LMICs innovative regenerative medicine can also be seen as a way of economically addressing both conditions in the long-term.

Especially HOs for SCI prioritise support for finding scientific cures, while many HOs for MD regard this as a desirable, though it is a contested subject. HOs for SCI from HICs found evidence-based medicine too slow and preferred to work with industry-oriented researchers that aim to market medicinal therapies. HOs from LMICs expressed worry about such permissive clinical trials, as they are suspected to be of low quality. But due to high healthcare costs, many patients are interested in them. Most HOs keep tabs on them, but China’s HOs refused to do so as they only recommended authorised clinical trials. In South Korea and Japan, homegrown clinical trials have shown much promise, but due to fabrication scandals, there have been setbacks. In Japan, at the time, the state was hesitant to allow clinical trials for SCI and MD.

Only in the West do HOs have a strong bargaining position and are able to influence the scientific research agenda directly; though in South Korea and Japan, HOs can do this through state mediation. HICs have information, facilities and financial resources that they can use to mobilise activism, in contrast with LMICs, where HOs have trouble attracting funding and where due to poor insurance conditions RCTs are not as attractive to industry. Mainly delegates from European and American HOs used notions of patient rights, individual responsibility and political initiative in explaining their workspaces, indicating that individual-rights discourses inhere to political identities widespread in Europe and the US. Although notions of patient rights are deployed in Asian HICs, local political discourses describe workspaces emphasising state guidelines, long-term collaboration and trust. Delegates from China and India mobilised much less human rights discourses in debate, rather emphasising the role of the state in providing financial support, countering discrimination against women and correcting resource allocation between rural and urban areas.

The individual-rights discourses used by HO delegates from HICs portray an assertive form of activism, expressed in discussions about political negotiations, collaboration with industry, their financial clout, their ability to steer research, their rights to lobby with government and their monitoring of ministerial tasks. It is doubtful that individual rights discourses are helpful in efforts to cover basic grass-root needs of disabled peoples in LMICs’ and in Asian HICs, especially as HOs look to the government for support and mediation in their social and medical endeavours. An HO from India remarked: ‘Poverty is a bigger problem to our government than is disability’ (Ghandi, 18–19/5/2015*). This means that expectations of governments are limited to meeting basic needs. When in pursuit of biomedical cures for SCI, there is no expectation that HOs can steer the development of scientific research by mobilising financial support via the state and charities. In India and China, the political and material contexts require a discourse that has covering basic needs as an endpoint; a pragmatism is adopted that favours a discourse conducive to the political identity of HOs within their political environment. Notions of human needs and trust may be of greater tactical use when requesting government and charity support, while individual-rights discourses may be more relevant to negotiations with industry. HOs in Asian HICs also refrain from individual-rights discourses, as a political culture of trust is more conducive to a relation of state dependency.