Having regulation in place can allow and justify clinical interventions that otherwise would be viewed as unauthorised and experimental. Being able to refer to the ‘right’ regulations therefore has immense redemptive force in clinical research applications. I speak of regulatory redemption when there is a need to emphasise the symbolic and ideological aspects of regulation: applying the ‘right’ regulation communicates a symbolic – not necessarily a realistic – commitment to responsibilities for patients and scientific development. In Part III, I use the notion of regulatory redemption to discuss the redemptive force of Japan’s regulatory reforms of regenerative medicine in 2014 (Chapter 6) and to investigate the redemptive performance of down-regulation advocated in international patient activism (Chapter 7).
The Redemptive and Performative Aspects of Regulation
Clinical research regulations have redemptive and performative aspects: redemptive, because they create the circumstances that enable clinical research and the development of innovative scientific products for the protection of the well-being and rights of patients; and performative, because the enactment of regulations vary. For instance, it can be slack, careless, absent or strictly audited. The politics behind regulatory boundary-making can easily result in a mismatch between the regulation and the domain it purports to address. In that case, the redemptive force of the regulation conceals a messy reality that may harm patients. For example, the creation of ‘constrictive’ regulation may help to enhance a country’s scientific reputation for political purposes and attract international collaborators, but it’s half-hearted implementation will neither protect the quality of science applications nor protect the safety of patients.
Part III shows how the enactment of the redemptive force of regulation needs to be understood in both the context of its collective global creation and that of its local meaning and functionality. In a world dominated by regulatory capitalism, regulators in their respective countries and regions tend to broker their regulation in relation to that of other countries and regions in such a way that they will gain a comparative edge. We saw in Part II how countries with relatively weak regulatory immunity struggle to maintain or improve their regulatory reputation, while countries assured of their regulatory immunity can afford to tolerate internal regulatory violations. In all cases, regulation is brokered to (positively or negatively) connect international regulatory values with those that sustain local practices. As a mode of coordinating regulatory values, I argue that the politics of regulatory redemption coordinates global regulatory regimes with regulatory capabilities on a national level, where its redemptive symbolism is mobilised in support of particular life science and public health strategies. As such, the regulation of regenerative medicine is co-produced both at international and national levels via the politics of redemption.
The politics of regulatory redemption is rooted in hegemonic powers and involve the status of reigning symbolic frameworks, such as those of ‘curing patients’, ‘technological fix’ and embedding regulation as ‘common-sense’ in a moral order, which is confirmed and nuanced in a person’s experience as real. But these hegemonic powers are changing and ‘power’ here goes beyond direct coercion and notions of false consciousness and ideology; it cannot be reduced to stakeholder theories, as it does not neatly correspond to the interest of one or another stakeholder or class. Its redemptive symbolism facilitates allegiance with the regulation by all involved, including the ideas of regulators, scientists, entrepreneurs, patients and other groups, such as notions of fairness, safety, freedom, care, obligation and truth, which develop and are reformulated in light of the ideals formulated in the discursive politics of regulatory redemption.
The Co-production of Regulation and the Politics of Redemption
Regulation is co-created globally, as its structures are produced dialectically through local and international pressures. This dialectic is negative and positive: negative, as competition and collaboration with the wider world puts constraints on the material conditions and conceptual apparatuses used in local regulatory design; and, positive, as it provides a resource for the generation of ideas and measures for national/regional regulatory strategy.
Regulatory documents embody and affect ideas about safety, risk, health and regulation in society, both at home and abroad. As the endpoints of a political process of deliberation, ratified regulatory documents have ‘the capacity to generate or enact effects in the social material world’ (Faulkner Reference Faulkner2012: 754). But the performative and redemptive force of regulation cannot be understood outside the worldviews they embody, their presumptions about risk and ethics, their regulatory status as law, clause or draft and the discursive language in which they are couched. The performance of regulation ensues from its institutional status and organisation: regulation performs through the social legitimacy endowed in it, its scope, its details, the expectations it enshrines and the ways in which its procedures, committees and audits compel enactment of its implementation by researchers, managers, patients and the regulators themselves (Faulkner Reference Faulkner2012).
The dialectic of regulatory reproduction means that the redemptive force of regulation has to be re-imagined, reconsidered and redefined through regulators and their networks. Within a national jurisdiction, regulation is brokered through informal and formal consultations and negotiation with stakeholders at various organisational levels, involving industry, scientists, patient organisation and the public (Abbott et al. Reference Abbott, Levi-Faur and Snidal2017), which in turn communicate with international regulatory agencies, professional organisations and governments. These international interactions can be bilateral and multilateral, through international and regional conferences and organisations of epistemic communities (Haas Reference Haas1992: 3; Salter and Qiu Reference Salter and Qiu2009: 47–48), but the extent of international consultation and collaboration varies. Countries with high regulatory immunity can afford to take the lead on authoritative international platforms, such as the ISSCR and ARMS, while scientists and officials in other countries regularly mention their low input (see also Zhang and Datta-Burton Reference Zhang and Datta-Burton2021). The observation of one leading Japanese scientist and official is telling: ‘Before the change of the [more permissive] law, the FDA always went to Europe to discuss the regulation, but now they come to Japan first’ (Interview Umeda, 27/2/2016*).
The credibility of regulatory performance empowers redemptive force and its norms and values are contingent on local practices. If they do not match, regulatory redemption becomes a matter of political strategy. What is crucial here is that, rather than based on local considerations of health needs, bioethics, clinical safety and scientific efficacy, local regulatory regimes are conditioned by standards and competition inherent to the global relations of regulatory production. This means that the integrity of any redemptive force exerted through research regulation is always already compromised by the international political strategies it is subjected to and creator of.
Regulatory Redemption and Its Transcendental Force
Regulatory authority enforces guidelines not only through bureaucratic powers, political strategy and through their appeal to local common-sense values. Rather, it is the way in which these are configured that creates an additional space for a symbolic order: because regulatory authority is symbolically located ‘above’ the members of its jurisdiction, and is rooted in the values of the community, it can gain transcendental force. Like ritual, regulation has the ability to reconfigure a vision of order or power in the world through fortified symbolic hierarchies. And as a strategic orientation for acting, regulation embodies the unexpressed assumptions that constitute the most influential actors’ understandings of the purposes, trajectories and places of its enactment. The institutionalisation of these regulatory assumptions, in fact, direct the socio-political boundaries of scientific discourses both in advance of and during the development and application of stem cell interventions.
The regulation of stem cell interventions both reverberates with and transcends the values asserted in local struggles, which cluster around socio-political positions ranging from ‘patient rights to safe therapy’ to the ‘freedom to choose medicine’ and from ‘the freedom to conduct research’ and ‘the need for regenerative medicine industry to battle ageing society’ to preferences for financing public health using other forms of socio-medical care. If we understand regulation as a process of clinical research vindication with complex ethical and safety guidelines and rules, involving committees of regulators and moral hierarchies that authorise ‘regular’ scientific research or not, we can start to appreciate the redemptive force of regulatory enactment. Although this force may meet with resistance among stakeholders and users, its authorised transcendental values are embedded in the polities of the reigning regulatory regime. To use a widely known example, when former US President Bush announced a moratorium on federal funding for embryonic stem cell research, the regulation proscribed and prescribed scientific behaviour but also embodied the outcomes of ethical struggles, conflicting economic interests, political ideals that gave meaning to the transcendental values embodied in the symbolic order.
As regulation cannot accommodate the needs of all stakeholders, it has to speak to multiple agendas without subscribing to them. Consequently, the enactment of regulation has to deal with the gaps between what practices are envisaged in the regulation and the needs and practices of its users. Such discrepancies are crucial junctures at which regulators extoll the redeeming functions of the regulation, directing its authority towards regulatory subjects. In other words, the reality of some users is always manipulated, but when such manipulation becomes a regular political mechanism, we need to speak of the politics of misrecognition.
Misrecognition
Regulation is usually thought of as fixed, formal, uniform in application and meticulously defined. But in regulatory capitalism, regulation is compromised by definition: it is situated, strategic and embedded in misrecognition. Inspired by Catherine Bell’s definition of ritual strategies, I claim that the strategic practice of implementing regulation is rooted in the intentional misrecognition of the practice it is enacting. In other words, the spirit or intention that justifies the creation of regulation or regulatory change is blind to the aims and practices of the environments it regulates, so that it literally ‘misrecognises’ what is happening on the ground. For instance, strategic down-regulation, also when called for by patients and industry, is blind to the practical consequences for patients.
The politics of regulatory redemption presumes translational work done that turns political strategy into regulatory guidelines and the redemptive beliefs that underlie it by shifting attention away from issues of medical practice, such as safety, profiteering, long-term care and actual patient needs to abstract ideals, such as those of ‘saving lives’ and ‘developing innovative science’. In other words, the symbolic value of ‘saving lives’ dramatises the idealised endpoint of clinical research and therapy provision and is ‘justified’ through regulatory redemption. But the politics of regulatory redemption is not about the ‘saving of people’s lives’ per se. Rather, its redemptive value is constituted in the belief that particular regulation will redeem what otherwise would be a deplorable or inferior medical practice. The authorisation of this belief and its juridical enactment in countless practices make for the ritualisation of regulation, regardless of how and if it is enforced to the letter. The reiterations and elaborations of the regulatory script and its underlying and embodied ideals by different stakeholders roots a diversity of ritualised regulatory enactments in both discursive and clinical practices.
Regulatory redemption, then, comprises both the ritualisation of regulation, involving the reiteration of formalities and its envisaged hallowed aims, and the strategic disregard of what actually happens on the ground. The regulation of regenerative medicine, whether up or down, may be incentivised by the aim to reduce public health bills, to stimulate the economy or to support other political targets. Here, regulatory facilitation is brokered by disregarding the existence of practices that do not fit the bill. In this sense, regulation is embedded in the misrecognition of what regulation is for and is biased about what it entails in practice. The ritualisation of regulation in regenerative medicine looks as if it is about fixed guidelines, rooted in the determination to protect patient needs and robust scientific protocol, but, and as we shall see, it is strategic, experimental and forces scientific development in new, and sometimes clashing, directions.
In short, Part III explores the redemptive aspects of the politics of regulation. Political ideologues, on the one hand, hallow regulation as promising and protective, while, on the other, it camouflages the political and economic interests behind discourses of ethical, medical and scientific progress. The politics of regulatory redemption then is violent in that it is blind to the actual scientific practices that it steers and the medical needs it purports to address.
Exploring the performance of the regulation 2013 reforms in Japan (Chapter 6) shows us how the political aims and ideas embodied in regulation support certain industries and sanctifies particular clinical targets, to gain a global competitive edge, as well as pursuing scientific, economic and public health goals. Regulatory reforms in Japan transformed the regulation of regenerative medicine from a cautious protector of patients and the scientific reputation to a scientific saviour of public health in Japan as an ageing society. An examination of the All Japan System, which symbolises these ideals, illustrates how the new regulation figures as both a socio-cultural text and as a performative subject. As a socio-cultural text, embodying various aims, it does not just tell us about the clinical trials and scientific research it regulates but also about the ethos that makes guidelines morally compelling and redemptive; as a performative subject, it actively shapes peoples’ conceptions of its aims at the neglect of other scientific and clinical needs.
Chapter 7 examines how international patient movements, inspired by organisations in the US and Western Europe, have come to see ‘de-regulation’ as a way to accelerate the translation of science into marketable medical products. Taking a cue from slogans of ‘freedom to choose medicine’ and the ‘right to try’ in the US, some influential international patient organisations tend to present ‘down regulation’ as a political way forward. Politically focusing on the redemptive aspects of down-regulation, they criticise those that see regulation as a safety valve and guarantor of reliable scientific research and clinical interventions as bureaucratic ritualism and defending the status quo (Braithwaite Reference Braithwaite2008). In an international context, however, this view is problematic. Conversations with and among patient organisations (health movements) show how regulation as a tool deployed by political movements can never be neutral in a world characterised by regulatory capitalism and inequality: its performance is contingent upon the material and organisational resources available to them and the population in general in a juridical mandate. The politics of redemptive regulation in international health movements risk reconfiguring healthcare developments by a misrecognition of actual patient needs and local practices.
The Ministry of Health, Welfare and Labour has been knocking on our door, asking when clinical application will begin!
For decades, Japan’s regenerative medicine has enjoyed regulatory immunity due to a regulatory regime that put reputation first. But after the first report of the derivation of induced pluripotent stem cells (often abbreviated to iPCs) in humans in 2007, a number of regulatory changes were introduced to accelerate the translation of iPSCs into clinical applications. In 2012, a regulatory overhaul was announced that would revolutionise clinical trials to address the health issues of Japan’s ageing population and Japan’s slumping economy. Rather than being grounded in healthcare needs and scientific safety and efficacy, I show how the new regulation was predominantly concerned with economic and national considerations as expressed in the Health and Pharmaceutical Promotion Strategy and the ‘All Japan System’ (AJS). AJS ideology, emphasising its ability to save lives globally, made Japan’s regulatory reforms redemptive to the life-saving therapies.
In this chapter, I show how a political strategy of this redemptive regulation harbours a discrepancy between the discursive aim of saving lives and that of regulatory protection of patients and good science. As explained in the introduction to Part III, the maintenance of such a strategy of redemptive regulation involves a continual misrecognition of what is actually going on in practice.
My examination of the dialectic between the international coproduction of Japan’s regulatory reforms and its implementation sheds light on how both Japan’s international research position has changed and how its science was affected at home, including scientific procedures and standards, research funding, priorities of clinical applications, structures of governance and fundamental scientific choices. I visited Japan from March–May 2013 and October–December 2013, when the regulatory overhaul was announced and prepared, and from January–March 2016, when the initial effects of the regulatory and procedural changes started to materialise. I spoke with scientists working in the field of regenerative medicine, including iPSC research, in hESC-research, tissue engineering, rehabilitation and the production of biomaterials in the Kansai region (CiRA), Institute Frontier Medical Sciences (IMFS) and Institute for Integrated Cell-Material Sciences (iCeMS), the RIKEN Centre for Developmental Biology (CDB) and in the Kanto region (Keio University and the Women’s University of Science and Technology). In addition, I spoke with experts in regulation, ethics and the social aspects of science and science communication. During these visits, we discussed the effects of regulatory changes and the AJS on their work, regenerative medicine in Japan and regulation in general.
Below I first describe the emergence of the AJS and the role of the state in the regulatory reforms. The second section examines how the regulatory politics of the AJS has affected the work of scientists by examining the collaboration among Japanese scientists, the frictions in the coordination of iPSC research, strategies used by scientists when planning clinical applications, constraints on scientific research and the ways in which scientists accommodate the AJS. After summarising the effects of the AJS on the work of scientists, the final section explains how the politics of regulatory redemption is based on a politics of misrecognition of what is actually going on and why this is important.
Regulatory Redemption and the Overhaul in Funding and Regulation
For years, in Japan, researchers had complained about the complex and time-consuming regulatory bureaucracy for stem cell research (Nakatsuji Reference Nakatsuji2007). But when, in October 2006, Shinya Yamanaka and Kazutoshi Takahashi ‘discovered’ how to create iPSCs using mice (Takahashi and Yamanaka Reference Takahashi and Yamanaka2006), things changed. The notion of cell-reprogramming – it seemed to reverse biological development – was received with global excitement, and when the reprogramming method was applied to human iPS the following year (Takahashi et al. Reference Takahashi, Tanabe, Ohnuki, Narita and Ichisaka2007), it propelled the government to action (interview Sato, 21/10/2008*; Hishiyama Reference Hishiyama2010).
IPS cells are made by ‘reprogramming’ somatic cells, such as skin cells. IPS cells closely resemble hESCs, which can be ‘differentiated’ into any of the few hundred kinds of cells of the human body. The process involved the introduction of a limited set of (initially four) ‘transcription factors’ and feeder culture to ‘fool’ the somatic cells into reprogramming or ‘reversing’ their development. Japan’s work on iPSCs not only showed the power of Japan’s science, it was also advertised as ethical. Some scientists contrasted iPS research with research using hESCs, which requires donated oocytes and the destruction of embryos, iPS was promoted as an inexhaustible source for producing healthy cells (Nishikawa et al. Reference Nishikawa, Goldstein and Nierras2008).
Even though Yamanaka and Takahashi were the first to ‘discover’ iPS, they had close competition from Jamie Thomson’s group at the University of Wisconsin, Madison. In fact, they both published their results on human iPSCs in November 2007 (Takahashi et al. Reference Takahashi, Tanabe, Ohnuki, Narita and Ichisaka2007; Yu et al. Reference Yu, Vodyanik, Smuga-Otto, Antosiewicz-Bourget, Frane, Tian, Nie, Jonsdottir, Ruotti, Stewart, Slukvin and Thomson2007). There was a realistic possibility that American researchers would claim a clinical first for iPS in humans. It was in this context that researchers asked for more funding for iPSC research and complained about Japan’s regulatory disadvantage (Hishiyama Reference Hishiyama2010).
Nearly instantly, a suite of regulatory innovations was introduced to re-channel funding into what official documents referred to as the ‘Japanese Research Team’ for iPSC research and regenerative medicine, to reorganise the system for scientific funding, to make attractive collaboration with industry through re-regulation and to lower the regulatory threshold for clinical trials (MEXT 2007). The Ministry of Education, Culture, Sports, Science and Technology (MEXT) increased its funding for iPSC research to 45 billion yen in 2008, a fifteen-fold increase over that of the previous year, and to 145 billion yen in 2009. In 2013, Prime Minister Shinzo Abe’s government committed ¥110 billion (about $1.1 billion) over ten years to iPSC research. Part of this amount was earmarked for ‘Yamanaka’s’ iPSC bank at CiRA, Kyoto University (Philippidinis Reference Philippidis2014).
Even before Yamanaka had received the Nobel Prize for his work on iPSCs in 2012, the Japanese government in 2010 had revised ‘the guideline for clinical studies using human stem cells’, expanding the coverage of the guidelines to include those for clinical studies using hESCs and iPSCs. In 2011, MEXT; the Ministry of Health, Labour and Welfare (MoHLW); and the Ministry of Economy, Trade and Industry (METI) had jointly launched the ‘Highway to the Realization of Regenerative Medicine’ to continuously promote research and development (R&D) for the realisation of regenerative medicine. This project culminated in the passing of the May 2013 Act for the Promotion of Regenerative Medicine, which obliged the government to promote regenerative medicine. A researcher-cum-regulator explained: ‘It is a political law meant to stimulate trust in the government and to stimulate industry to invest’ (Imano, 9/3/2013*).
As explained in Chapter 2, two other acts followed: The Act on the Safety of Regenerative Medicine (RM Act) (2013 Act No. 85) and the Revised Pharmaceutical Affairs Law: The Pharmaceuticals and Medical Devices Act (PMD Act) (2013 Act No. 84), both of which were enacted in November 2014. These acts have altered the conditions for clinical application of regenerative medicine. The PMD Act introduced a specific regulatory framework for regenerative medicine products: it stipulates that the PMDA and the MoHLW provide for a conditional time-limited approval system for regenerative medical products. After exploratory clinical trials have demonstrated ‘probable benefit’ and ‘proven safety’, the product is given conditional, time-limited marketing authorisation (PMDA 2014; Azuma Reference Azuma2015). Allowing marketing without scientific evidence through conventional clinical trials, the new regulation attracted the interest of large companies, such as Sumitomo, Athersys, Mesoblast and Cytori Therapeutics, within a few months (Accesswire 2014).
Apart from regulatory innovations, new infrastructural policies were introduced to turn iPSC research into a success. The government promoted the creation of biomedical clusters, Sūpā Tokku (special disciplinary areas or networks), expanded IPR facilities and established support mechanisms for the collaboration between research institutions and industry. The new funding policies, formulated by the Headquarters of Healthcare Policy established in 2014 under the Cabinet Secretariat, integrated medical R&D budgets to concentrate on priority projects such as iPSC research proposals (Kantei 2013). The budgets of MEXT, METI and MoHWL were consolidated in the newly established Agency for Medical Research Development (AMED) from April 2015 (Sengoku et al. Reference Sengoku, Mitsuya and Yoshimi2015). The new policies entitled ‘Initiatives under the Project for Japan Translational and Clinical Research Core Centers’ also promote specialised support for patent applications and education in translational research (Headquarters of Health Policy 2014) and the new Patent Act allowed the application for patent extensions for regenerative medicine for up to five years (Japan Patent Office 2014).
Crucially, according to the PMD Act, AMED allowed the reimbursement of newly approved regenerative medicine products, including conditionally approved products. NIH-insured treatment could also be combined with unapproved regenerative medicine products or ‘evaluation treatment’ if MoHWL assigns it ‘Advanced Medical Treatment’ status (Health Insurance Act Article 86, cited in Azuma Reference Azuma2015: 126). Therefore, based on the expectation that the product works, Japan’s insurance system covers part of the costs, and the patient contributes 10–30 per cent of the cost, albeit capped at around ¥100,000 (Anonymous Reference Anonymous2015). Evidence for the conditionally approved therapy is required within a maximum of seven years, after which the regenerative product is unconditionally approved or rejected. According to Abe (9/03/2013*), these policies were expected to accelerate the application and commercialisation of regenerative medicine and iPSC research in particular.
Rather than maintaining its regulatory immunity, prioritising patient safety and science quality, the regulatory reforms were based on a polity of regulatory redemption that would shorten the regulatory pathways of regenerative medicine to the clinic. The financial and regulatory support for the commercialisation of science, including the introduction of a new insurance strategy and the shift from support for laboratory research to clinical research politically prioritised regenerative medicine above traditional branches of science and altered the standards and methods used in the production and evaluation of techno-scientific products. This organisational and material shift was accomplished through the political support for a vision for the AJS.
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.
In the following extract from a CiRA Newsletter (CiRA 2012), Professor Toshihiko Hoshino describes the AJS as the redemptive force behind the regulatory overhaul:
In the future, cell therapy using iPSCs may be able to cure intractable diseases and lifestyle-related diseases. In order to meet the expectations and hopes of people who have such diseases and to realize life innovation originating in Japan, we will establish a system to bring together a lot of wisdom and promote iPSC research more effectively.
A collective effort would mobilise resources in support of the long-term vision of iPSC cures.
A long-term vision will enable us to systematically secure intellectual assets. On this basis, the results of short- and medium-term projects of 3 to 5 years, furnished with various competitive funds, will be organically linked and lead to even greater results. Thus, intellectual assets originating in Japan will be used by all humankind. In turn, the chances of Japanese assets being utilised will expand.
The realisation of the AJS vision required overcoming institutional barriers to research promotion:
We will work to improve the research base while securing intellectual assets and striving to overcome institutional barriers related to research promotion. We will promote all-Japan collaboration with related ministries and agencies and industry, and lay the foundation for returning the results of iPSC research to society.
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.
How Did the ‘All Japan System’ Politics behind the Regulation Affect the Work of Scientists?
In July 2013, Masayo Takahashi from RIKEN-CDB received permission from the MoHWL to conduct a clinical iPSC pilot-study using iPSCs for age-related macular degeneration (AMD), news that soon spread across Japan and around the globe. In a few days’ time, the study had recruited over one hundred patients, even though it was just a safety study; efficacy was to be tested in a next phase. According to a scientist working on the project: ‘They are all in support of the study, because they want iPS to succeed!’ (Ohashi, 29/3/2013*) This was the spirit of the ‘All Japan System’ speaking – the spirit that made the new regulation redemptive. But how did its politics regulate and affect the work of scientists?
This section explains how the AJS’s politics of regulatory redemption affected research practice. It examines the dialectics between AJS and iPSC research in respect to: (a) research collaboration, (b) research coordination, (c) research options and considerations, (c) constraints on science and (e) working with and around AJS politics.
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:
‘All Japan System’ means that all the best scientists [in Japan] collaborate to produce good science applications in collaboration with the best scientists in the world.
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:
The ‘All Japan System’ policy is a problem, as it likes to have everything from bench to bedside taking place in Japan. Hence, [the transplantation of iPS-] RPE cells is not important because of its value to the patient, but for creating a seamless line from bench to bedside in Japan.
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:
There are too many political problems for collaborating with China now. Apart from that 90% of the JST focuses on All Japan, and as CIRA is the hub of All Japan, they cannot go to China. Nevertheless, Japanese researchers individually try to get overseas. Prof Shirakawa will go to Another [anonymised] University, where he wants to do translational research with overseas partners.
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:
They do not collaborate! CIRA collaborates with FBRI [Foundation for Biomedical Research and Innovation] in Kobe. The Medical School does not accept iPS. Officially there are collaborations, but in practice, we do not see them. There has been no discussion about how to develop a clinical application of iPSCs in Kyoto, and Kobe is only two hours from here …. IPS does not benefit the traditional Medical School in Kyoto University.
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:
Currently safety and efficacy studies have to be done before clinical trials can start, but this is going to be reduced to safety studies alone. This is because iPSC applications are expected to be effective. The regulation will be about ‘regenerative therapy’ [saisei-chiryō] as ‘regenerative medicine’ [saisei yiryō] is not a correct expression: we do not know yet if it is regenerative [the emphasis is that of the interviewee].
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:
For the new regulation, the three ministries [MoHWL, MEXT, METI] are working together. After the clinical research, we can have a clinical trial, which will be easier than before. We can still do the research at the Hospital as Advanced Medical Therapy [sentan yiryo], which includes insurance of both patients and doctors.
A great step forward, the researcher explained, is that the RM Act facilitates the outsourcing of cell processing:
Before the doctors had to process the cells themselves. This [RM Act] is a big step forward, as doctors have no time to do this. Now they can outsource. This is why she set up a company [Healios], and asked the company to take care of it. It also made possible to take things outside Japan, but that is not the purpose of the law.
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:
We know now that using iPSCs you can create neurons effectively. The standardisation of CiRA’s way of working concerns good methods of differentiation and multi-potentiality and checking whether the iPSCs have cancerous effects. CiRA is now looking into the safety of the iPSC derived neuronal stem cells.
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:
The standardisation of iPS is a very important topic of discussion now. There are two ways of thinking about standardisation: having the cell line as standard or having the assay as standard. Yamanaka Sensei had wanted to use one iPSC line as a gold standard and compare others to it. But this did not go very well, also internationally. But now, Yamanaka wanted to make the assay he uses standard. But it turns out that Life Technology’s assay is strongest [more competitive]. Life Technology is an assay from American reagent producer Invitrogen. Applied Biosystems merged with Invitrogen (ABI), forming Life Technology. Life Technology has internationally the strongest assays. The reason for this is that there is the International Stem Cell Bank Initiative (ISCBI), run by Austin Smith [sic] and others in the UK; they use the methods created by ABI. And this now is naturally applied to iPSC research.
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:
For example, last year we finished the study, and the results seemed to be pretty good. But suddenly [they said] ‘Okay, we made a new plasmid. You have to change it.’ We needed to use a patent from their medical company [Academia Japan] to improve the efficiency of iPSCs by inhibiting the p53 function [a tumor suppressor] – AJ006. We should be All-Japan, and use a Japanese patent. But then we have to throw away the earlier test! They don’t care: it [the test] should have nothing to do with their [wish to publish a] paper. I just have to follow suit.
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:
Yamanaka does not care what happens to his knowledge, or whether people in the USA use it – he is more in the USA than in Japan. There, he can also easily use embryonic stem cells. This is problematic, as Japan Academia tries to market his methods widely.
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.
In 2013, a list of planned iPSC applications was announced at CiRA. It included Jun Takahashi’s project to treat Parkinson’s Disease (PD) using iPSCs. Takahashi was one of the many researchers who supported the use of the so-called Yamanaka-factors, -assays and -culture media, but, according to Tanabe, a researcher on the project, they also liked to have the freedom to experiment with his own (Tanabe, 15/11/2013*). In 2014, Takahashi received permission from MoHWL to use iPSC-derived dopamine neurons (iPS-DN) in a clinical study for Parkinson’s Disease, initially involving autologous iPSCs. His team had resolved problems related to the mass-culturing and safety of cells for transplants, and with the help of the large pharmaceutical company, Dainippon Sumitomo, he hoped to receive the go ahead for a clinical trial in 2015 through the PMD Act (Yamasaki and Arai Reference Yamasaki and Arai2014). But for scientifically unclear reasons, it was decided to use a different cell source for his clinical study: The major histocompatibility complex (MHC)-matched iPSCs from CiRA’s homozygous iPSC stock. According to Tanabe, the application of iPS-DN was likely to create only a minor histocompatibility antigen (MHA), which is known to cause problems of immunological rejection much less often than that of MHC. The new situation created a dilemma for Takahashi: He had wanted to forge ahead with a clinical study using autologous iPSCs to create a proof of principle. But, conform the AJS-vision, it was decided that the clinical study had to use CIRA’s iPSC-line stock, which made turned this into an allogeneic application. Tanebe explained that this decision had not satisfied the Medical School and Kyoto University Hospital (KUH): KUH had had in mind an autologous application, and it had major reservations about using allogeneic iPSCs (Tanabe, 12/02/2016*). Though some colleagues ascribed this reservation to the ‘conservative’ attitude of KUH, others said KUH feared the enormous reputational risk if the first in human applications of iPS-DN would fail.
Although the guidelines for clinical studies are thought to be less stringent than those for commercial clinical trials, the cell lines used in Masayo Takahashi’s clinical pilot study of age-related AMD using autologous iPS-RPE, the world’s first in human clinical trial, required whole-genome sequencing: the original cells, those differentiated, and those in vivo, all had to be sequenced, and a listing of all their mutations had to be provided to make sure that the cells were stable and safe. But once given permission, the cost for quality control amounted to 50 million Yen ($500k), which was covered by MoHWL. But in late March 2015, it was announced that the RPE-cells of Masayo Takahashi’s second patient showed mutations, after which the clinical study was halted (IBRI 2015). By then, it had become policy to use allogeneic cells from Yamanaka’s iPSC bank. Using autologous cells, it was generally argued, takes much time and is expensive. But Takahashi declared that it was she who had decided to stop the autologous pilot-study: not so much because of the mutations, which she had expected to occur, and not because she had been told to do so, but because of the new regulatory options supportive of clinical trials that had become available since November 2014 (Knoepfler Reference Knoepfler2015).
Other researchers, however, argued that in her place they would have continued to conduct clinical research first, but now using allogeneic iPS-derived RPE-cells to avoid genetic tumorigenicity. Paid for by CiRA and MoHWL, she could use CiRA’s GCTP-accredited cells for clinical research, process them with Haelios, the company she worked with, and create a proof of principle. But Takahashi went ahead with the clinical trial supported by the pharmaceutical giant Sumitomo Dainippon Pharma Co. Of course, a colleague explained, industrial companies rarely make large investments for the sake of a scientific study alone (Kodama, 6/3/2016*). Industry likes to focus on factors related to safety of the production process and marketing; they like to have reliable starting materials (Umeda, 27/2/2016*).
The advent of the AJS-vision, then, has meant that an increasing number of scientists decided to use iPS in addressing conditions in collaboration with industry. As the ultimate aim was commercialisation and mass-production, there was a push not just for the clinic but also to collaborate with industry and to use ‘off the shelf’ allogeneic cells, preferably from Kyoto’s iPSC stocks. To accelerate this effort scientifically, and to facilitate the ideal of All-Japan production, CiRA methods, resources and standards were shared.
The ‘choice’ between the pathways of clinical research and clinical trials depends on various factors, ranging from the planned medical intervention and the PI’s location and collaborating hospital to the PI’s relation with CiRA. Decisions involve complex considerations, including issues related to cell sourcing and use (autologous, allogeneic), access to funding (through government funding, industry investment, grants.), management (e.g., engaging a company or not), use of culture media, assays, vectors, etc., ease of acquiring authorisations, availability of facilities and their quality and the onerousness of regulatory pathways.
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:
On Thursday-mornings all lab leaders have to present their work in Japanese and in English. Before this was very useful. But there is a lot of competition. Also, many have links with companies, so they are bound to secrecy. Some do not even want to reveal the molecules they are working on.
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:
I have a company and he has a company. We are in competition, so I need permission to collaborate.
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:
The Sendai virus works outside of the nucleus, but Yamanaka uses an episomal plasmid, which in principle can be integrated into the chromosomes.
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:
The design of the iPS-pilot at CiRA will provide authority, and this will help with getting PMDA permission for the clinical research/trial. Using the same design, we can do a PI-led IND (Investigational New Drug) application.
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:
Today I had to go to a managerial meeting with companies, then to a medical department meeting at the Medical School, and then we had team meetings. Now, I meet you and I also need to speak with my assistant about CPC as he needs to leave early.
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:
CiRA is run hierarchically: the top decides what PIs do and with whom they collaborate. CiRA also tries to determine what happens in other labs that use iPS. This is because Yamanaka wants his own products standardized. But it is important to participate in the International Stem Cell Banking Initiative (ISCBI), to discuss how to define pluripotency. Yamanaka was not interested even though Japan paid for Japanese scientists to be part of it.
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:
Tissue engineering gets little grant money for research: it all goes to iPS. But researchers from CiRA come to my lab for advice …. I do not get money for that!
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:
Yamanaka should never have spread doubt about the ethics of ESC by comparing his daughter to an embryo. hESC-lines are the Gold Standard for iPS; they were there first. So you do need to research them.
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:
Just use one good cell-line can produce lots of cells for all patients all the time. This solves both issues of costs and storage. Later you can work on further technological improvements regarding assays, efficacy – in the meanwhile you use immune-suppressants. You can always switch to iPS afterwards.
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:
There are some rough standards for classifying pluripotency, but there are no standard measures for infections: In a chemical drug, it is very easy to disinfect, but we cannot kick out any germ out of a cell or a biological …. You cannot use the same template as for drugs. But with the use of IT, sensing technology, and other methods you can measure all the parameters and mediums to check the metabolome, PH-sensors, CO2-sensors, and so on. By combining the results, we can assure the quality of the product.
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.
The Politics of Regulatory Redemption as a Politics of Misrecognition of What Is Going On
Insight into the AJS politics of regulatory redemption sheds light on how the regulation of regenerative medicine misrecognised the scientific reality effected by the regulatory reforms as collective and collaborative, as a Japanese scientific feat and an attempt to save the world to the glory of Japan, as a panacea for an ageing society and as rescue for patients disabled by serious medical conditions ranging from AMD to PD.
We saw how the AJS matched the regulation with its organisational policies but could only do so by misrecognising what was going on in the field. Rather than a united effort of the ‘Japanese Research Team’ on the road to scientific success, we saw the rise of a regulatory framework for clinical trials whose approval mechanism presumes the success of applications developed in the hierarchically organised, privileged iPS-hubs. In addition to the hurry to bring iPSC therapies to the clinic, we also saw an insistence on branding ‘Yamanaka methods’ as knowledge assets, a move that frustrated many of those involved in the research applications to the extent that hospitals distanced themselves from taking responsibility for applying them.
The new regulation aimed to facilitate both clinical research and clinical trials in the field of regenerative medicine and beyond. Although the regulation may have become more ‘permissive’, it is no less complex. It required researchers to acquire expertise in a wide range of areas related to the new politics of cell-sourcing and use, access to funding under AMED, extended administrative management, the tactics of using culture media, assays and vectors politically, becoming savvy about acquiring knowledge assets, the complex rules for applying for authorisations, the negotiation of regulatory pathways and the lobbying for the required laboratory-facilities. In the light of the AJS vision of global success of iPSC research and the wide range of skills and efforts needed for clinical iPS applications, scientists were pushed into the arms of industry and the application of ‘off- the-shelf’ allogeneic cells using CiRA’s iPSC stocks. Although collaboration with industry might mean financial and managerial support, the pressure can distract their focus on research, and contracts are likely to include secrecy clauses that shackle scientific discussion. The various rules introduced around iPSC line usage, assays, feeders and culture media led to obligatory collaboration, on the one hand, and precluded possibly fruitful exchanges with other scientists, on the other. As a result, important scientific discussions stopped taking place, pushing scientists to join more internationally oriented institutions and discussions. As it focused on presenting the world with life-saving regenerative therapies, the AJS-vision blinded its proponents to the scientific and professional needs of researchers, without reflection on whether patient needs were best addressed through iPS or other technologies.
All in all, an orientation to basic research, the cultivation of a wide range of life-science disciplines in the field of regenerative medicine and collaboration with specialised companies made space for a research orientation to clinical iPSC applications in collaboration with large industry and venture capital. The reconfiguration of funding and resources, the leadership of CiRA and the obligation to follow Yamanaka methods had the effect of alienating other leading researchers in the field of regenerative medicine. Scientists in iPSC hubs said they enjoy conducting scientific research and take pride in contributing to their team, to science and to human health. If needed, they spend evenings and weekends to attain their goal. They like getting their heads around all aspects of their research tasks, exploring alternative methods, honing their skills and getting feedback from colleagues. Becoming part of an iPS production line for Corporation Japan, however, was not what most of them had signed up for.
The imperative to translate (Harrington and Hauskeller Reference Harrington and Hauskeller2014) research outcomes into clinical applications forces scientists to make a strong case for their experimental models to compete for funding. Although regulation for clinical iPS trials has become more permissive, there is an extreme pressure to be successful, as failure would reflect disastrously on the institutions involved and, crucially, on Japan’s regulatory system. It would also mean letting down the ‘Japanese Research Team’ and the death-knell of Japan’s already weakened regulatory immunity. The pressure on scientists to engage in the clinical translation of iPS research, on the one hand, and the stringent checks and verification of the research protocol, on the other, create great pressures along the translational pathway. The resultant rollercoaster of forced promise and necessary failures together with the scientific and organisational constrictions imposed by AJS cannot be conducive to the kind of scientific understanding that Yamanaka had acquired before he became Japan’s scientific saviour.
Nevertheless, since the introduction of the regulatory reforms, now ten years ago, there has been a gradual move away from overhyping iPS and other regenerative medicine products. PMDA review reports (PMDA undated) show that the clinical studies that were used to justify conditional approvals suffer shortcomings. Cyranoski et al. (Reference Cyranoski, Sipp, Malik and Rasko2023) show how deficiencies in trial design undermine the rationale for both on-market clinical use and insurance reimbursement, rendering it unclear as to whether trial effects (including severe adverse reactions and deaths) are a result of biomedical intervention or the, often, invasive operation itself. Furthermore, the long period of post-marketing studies that proponents of conditional approval believe can generate proper evidence usually lacks randomisation, blinding and independent analysis, potentially lengthening a period of experimentation. There is evidence that the PMDA has started to take a stricter stance on regenerative medicine product approvals, demanding more evidence and giving far fewer regenerative medicine products conditional approval (Nomura Reference Nomura2021; Cyranoski et al. Reference Cyranoski, Sipp, Malik and Rasko2023). This makes the question of whether accelerated regulation helps company profit, scientific knowledge or patient health even more poignant. Posing it becomes crucial to the issues of why and how a society might want to fund and support the science community. If doubts are shoved aside amidst feverish global competition, one might have to ask what countries that compete by brokering their research regulation to their own advantage have to offer to patients. What do patients want, and more importantly, need?
Dr Wise Young said: ‘We’re working hard on phase three for a “miracle cord” whatever, whatever’, I won’t go into details’. So, they’re recruiting people in India for phase three clinical trial applications in 2016. In the mean while they have decided to do phase 2-B trials in China, India and US. But When you start a phase 3 trial, you first need to have completed a successful [phase] 2-B trial, right? I did not see any publication about it …. I just want to know from the people who know him in his own country [the US]: Had he passed a successful phase 2 trial, would he have come to India?
Introduction
This chapter examines the ideological dimensions of regulation as safety valve and guarantor of reliable scientific research and clinical interventions against the background of the expanding ‘freedom to choose medicine’ (FTCM) movement as a force against the pharmaceutical industry and the strict regulatory requirements for clinical trials in an international context. From the point of view of an increasing number of health activists in wealthy nations in Europe and North America, the world’s neoliberal economy pits the interests of medical industries against those of patients (e.g., Fisher Reference Fisher2007; Batt Reference Batt2017). In the US, strict FDA regulation for clinical trials and the marketing of medical products would continue the national monopoly of the pharmaceutical industry on the drugs market. It would leave little space for competitors with innovative solutions to serious patient conditions.
The urgency of this situation became manifest when patient movements increased their public visibility in the media in the 1990s (e.g., the film Dallas Buyer’s Club), campaigning for an acceleration of the clinical development of new drugs, ranging from medicine for orphan diseases to intractable conditions such as HIV (Epstein Reference Epstein1996). Critical theory holds that the new health activism no longer passively waits for the hegemonic international life-science industry to produce cures. Instead, health activists demand that patients’ wishes are accommodated and healthcare products are made available earlier (Salter et al. Reference Salter, Zhou and Datta2015). In this view, the redemptive force behind regulation is a myth. Rather than protecting patients, it hinders the development of life-saving drugs and therapies; and rather than enabling the clinical translation of medicine through scientific clinical trials, it slows down the efforts of industries that genuinely support patients by focusing their research on early marketing rather than abstract scientific questions.
In this century, a trickle of patients opting for stem cell therapies abroad grew into a vast global movement of stem cell tourism (Song Reference Song2010; Chen and Gottweis 2011; McMahon Reference McMahon2014; Salter et al. Reference Salter, Zhou and Datta2015). At first, countries in Latin America and Asia became favourite ‘therapeutic’ destinations. Companies of all sizes began to champion the case of hopeful patients and invited them to receive the ‘most advanced’ stem cell interventions, both paid and unpaid (Brown and Micheal Reference Brown and Michael2003; Petersen et al. Reference Petersen, Seear and Munsie2013, Reference Petersen, Munsie, Tanner, MacGregor and Brophy2017; Bianco and Sipp Reference Bianco and Sipp2014; Turner and Knoepfler Reference Turner and Knoepfler2016; Sipp et al. Reference Sipp, Caulfield, Kaye, Barfoot, Blackburn and Chan2017), some even using ‘recruiter patients’ to persuade other patients to spread the word (Patra and Sleeboom-Faulker Reference Patra and Sleeboom-Faulkner2009). Growing access to the internet and global travel (Keck and Sikkink Reference Keck and Sikkink1998) enabled increased numbers of patients to join the swelling flow of medical and stem cell tourism, and the interest in the global provision of drugs and therapies grew exponentially.
Patient organisations began to compare regulation for clinical trials, prices for interventions and the experiences of patients and invested efforts in international activities. These increasingly involved knowledge exchanges and local support for patient movements in LMICs. Thus, the International Organization for Muscular Dystrophy (IOMD, pseudonym) ‘reaches out to countries where limited information about Duchenne Muscular Dystrophy is available’ by facilitating the exchange of information about fundraising and lobbying activities among (associate) member organisations, while the US-based International Organization for Spinal Cord Injury (IOSCI, pseudonym) aims to unite and empower the international spinal cord community and to cure paralysis through advocacy, education and support for research.
Although Western patient movements established international branches, their agendas were underpinned by medical and regulatory goals that suited their societies. This led to frustration, as not all countries share the tendency of Western patient organisations or, as we shall see more aptly, health organisations (HOs) to assert their agency through individual initiatives and activities to gather information aimed at accelerating the translation of science into clinical applications that can cure patients with serious, protractive diseases (Rabeharisao et al. Reference Rabeharisoa, Moreira and Akrich2014). For instance, a representative of the IOMD wondered why Asian organisations do not accept their scientific information, believing that: ‘It would help them understand what science can or cannot do for them’ (Van Kindel, 16/2/2015*). Although this representative found it ‘understandable that people at war, the unemployed, or the abused may not be able to become active’, they found it ‘puzzling that countries do not collaborate with us more closely’ (Van Kindel, 16/2/2015*). Nevertheless, experience told them that, within Europe and the US, there are differences in activism cultures. In Scandinavia, they explained, there are high tax levies, so parents often assume a passive role, expecting the state to provide welfare. By contrast, parents in the US take a more active role, whilst in the Netherlands they emphasise enjoying life in the present. For activism, they concluded, ‘you need an entrepreneurial culture; where it is lacking, such as in Eastern Europe, parents tend to wait for government assistance’ (Van Kindel, 16/2/2015*).
HOs activities have increasingly included efforts around knowledge gathering, taking initiatives for research, managing records and data and looking into scientific research. Health organisations concerned with muscular dystrophy (MD) and spinal cord injuries (SCI) (Rabeharisao Reference Rabeharisoa2006; Sakai Reference Sakai2014; Anderson and McCleary Reference Anderson and McCleary2016; Epstein 2016; also see Brown et al. 2004) are no exception. But international HOs have come to focus on issues relevant to some Western societies only. For instance, various HOs in the US campaign for patient freedom to choose medicine (FCTM) include medicines that have not received permission for clinical trials or marketing by the relevant authorities. Supporters of FCTM, including US right-wing political groups such as the Illinois-based Heartland Institute, propose that, rather than the government, patients and doctors should make their own health-care choices, as it ‘would lower the cost of pharmaceutical drugs while expediting the approval of potentially life-saving treatments’ (Herrin Reference Herrin2020).
A core concept in FTCM is that clinical trial sponsors should be allowed to begin selling investigational products to patients while phase 2 studies are still underway to save the lives of patients (Madden Reference Madden2010). Criticising that ‘prohibitive’ regulation as bureaucratic, lobbyists support ‘deregulation’ as the expression of liberty and responsible health choices. Rather than protecting patient interests, then, in this view clinical trial regulation in the US protects a particular kind of clinical science. For supporters of FTCM, the, ‘deregulation’ will facilitate and expedite the marketing and, therefore, availability of life-saving therapies. From an international perspective, however, this redemptive view of deregulation can be questioned.
Questioning the ‘Redemptive’ Nature of Down-regulation in an International Context
Western individual human-rights discourses defined by the global privileged may lead to the ‘normalisation’ (Canguilhem1989; Foucault Reference Foucault and Davidson2003) of a reality defined by the globally powerful, failing to take into account the position of less powerful groups in the world. Considering the societal roots of disability (Shakespeare Reference Shakespeare1993) and biological reality of impairment, it is not likely that all impairments will be mended and all genetic ‘abnormalities’ prevented. ‘Disability’, therefore, is not something to get rid of as soon as possible but to be accepted and accommodated by society. As such, the identities of local health movements from the South need to be incorporated in order to counter the hegemony of the ‘Northern’ disability discourse (Meekosha and Soldatic Reference Meekosha, Soldatic, Soldatic and Meekosha2014: 24). Identity is not merely a social construction or by-product of power; it is also ‘a way of inhabiting, interpreting and working through an objective social location and group history’ (Alcoff Reference Alcoff2006: 42). Other-ability movement scholars, such as Tobin Siebers (Reference Siebers2011), view other-abledness as an embodied identity and define ‘disability’ as an ontological category. The extent to which improvement can be identified and realised, then, depends on the availability of resources, the socio-political environment and concepts of identity.
In the context of regenerative medicine, we must ask whether stem cell therapies occupy the top of the wish list of patients, as seems to be presumed by life-science industries. Where stem cell therapies are presumed to address patient needs, we must ask if down-regulation is always in their favour. Globally, there is no transcendental authority that can tell patients which countries have adopted the ‘best’ regulation, and which therapies are ‘safe and efficacious’, ‘extortionate’, ‘placebo’ or ‘snake oil’. This chapter aims to recognise the wishes and needs of HOs that represent patients with different possibilities and embodied identities in different parts of the world.
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.
Challenges for MD and SCI Organisations and Political Governance
The discussion of the challenges faced by HOs allows us to reflect on the universal benefits and feasibility of Western modes of political activism in different countries. HOs for MD and SCI share various challenges pertaining to treatment: there is a lack of knowledge of patient medication, and symptoms that affect treatment such as pressure sores, numbness, bladder- and bowel-management and long waits for clinical trials. They also share problems related to social infrastructure and information, such as an accurate registration of persons with disabilities to provide adequate care and to decide what kind of research is needed and public awareness of disability. But they also have different priorities. Although all the HOs referred to the need for medication and appropriate equipment that allows for bladder- and bowel-management as a most urgent priority, only MD organisations emphasise the prioritisation of greater awareness of prenatal genetic testing and the need for research into pain management and methods to raise the quality of life, while SCI organisations refer to the need for housing, education and employment after hospitalisation as essential to the return of persons with SCI to society. In other words, the first focuses on the medical condition, while the second aims for ‘return to society’.
Daily life entails different challenges for the two conditions. As MD is diagnosed from an early age and indicates a low life expectancy, many persons with the condition identify with MD and belong to a MD community. Persons with MD tend to be represented by their parents, which is why many MD organisations are parent organisations, such as the Parents of Patients with Muscular Dystrophy Organisation (PPMDO). It is usually parents or carers who enquire about clinical trials. This situation contrasts with the tendency among individuals with SCI, who have a relatively high life expectancy, independence and mobility. However, many persons with SCI avoid belonging to an SCI community. One SCI HO delegate said:
Most people don’t actually perceive themselves as being disabled; it’s an acquired condition. I’m still me; I still support Man[chester] United; and I want to go down to the pub with my mates and scream and shout about football and call the ref a ‘whatever’…. One of my trustees went on holiday and had to source an accessible house. He was horrified when he discovered that in the property next door there also was a SCI person …. He said he hated it.
Often acquired in an active life, SCI necessitates the sudden adoption of a new lifestyle. Many persons with SCI try to maintain their pre-SCI social life and independence.
The HOs for MD and SCI also have different relations with clinicians and scientists. Both SCI and MD HOs prioritise immediate needs. But while SCI organisations generally liaise with scientists directly to find a cure, contacts between MD organisations and the science community are often mediated by family members and involve various kinds of research ranging from improving the quality of life, such as by improving heart and breathing function, to potential life-saving interventions, such as experimental gene-therapy.
The lobbying of HOs can be defined by the kind of ‘workspaces’ they occupy. Workspaces here refers to the geographical spaces in which HOs can exert their influence. The ‘local’ workspaces of HOs are subject to a range of political factors, including public support, competition from other HOs, political status and institutional sources of fund raising, such as subsidies, charity and tax. The transnational workspaces they move in are shaped by the availability of resources both locally and internationally and by the politics that drive HOs and transform them. Some HOs complement each other, while others have similar or overlapping functions. For instance, the SCI-network (SCIN) in the UK focuses on fundraising and scientific research, while other SCI organisations deal with more practical services.
Regional HOs and HOs with similar functions sometimes compete for the same resources. Thus, the UK in 2015 had a congestion of nine different SCI charities, which limited their scope for fundraising and research activities. Some countries just have branches of international organisations, such as Sri Lanka, which has only very small grass-root groups and the PPMDO (pseudonym). The status of HOs as non-political organisations (NPOs), non-governmental organisations (NGOs) or grass-root organisations greatly affects the workspaces of HOs: usually, charitable trusts are tax-exempt and government-supported NPOs prohibited from political lobbying, while NGOs may both receive funds and be allowed to lobby. But definitions of NGOs are highly variable. In both India and China, NGOs experience difficulties when trying to register, and restrictive policies have been put in place to stymie international capital flows associated with Western political influence (L.A.W. 2015; CDB 2016). Conditions for charitable gifts vary, too: taxes on legacies, for example, are low in the US but high in Japan (Yamakoshi Undated). The variability of this institutional landscape, as we will see, is closely related to HOs’ budgets and agendas.
The extent to which HOs enjoy support and authority in a country depends on the socio-political space available to them. Most HO/NGOs in China and India focus their activities on information sharing, advising, and offering practical support. Struggling to acquire state recognition and funding for the operation of their organisations, they are usually vulnerable to government interference and are in a weak position when negotiating with industry. A leader of an Indian MD HO illustrates this:
In our country, I don’t think patient organisations have due recognition by the government. They are not viewed as influential bodies or necessary, which reflects on our voice. So, we have to make the government understand what the patient organisation means first …. The space available to interact with the government is very limited.
Other HOs receive recognition and support from the government and have some authority to make decisions about financial spending. Examples are large government NPOs, such as China’s Disabled Persons Federation (CDPF 2016, 2021). Such organisations can advise the government about disability classification systems on the basis of which financial and material resources are allocated to hospitals and patients but have very little clout and hardly any monitoring power over patient activities and needs. More powerful HOs, usually located in HICs, can spawn into large-scale, international networks. They are able to negotiate funding and to monitor government support, steer scientific research in negotiation with academia and industry and forge their own social identities.
Delegates from HOs for SCI in HICs discussed collaboration with industry in terms of asserting rights, self-empowerment and lobbying with governments. For instance, one American delegate explained:
We’re not necessarily growing ours, but we’re spawning other organisations so people get the bug to advocate. We have a toolkit – you don’t have to even leave the house to advocate – you can work on legislation, you can send letters you can make phone calls. This is important and it gets things done; some of this work, to take up an advocacy stance empowers them.
An Indian MD HO, however, emphasised financial requirements:
In developed countries, the patient groups are capable of funding the research towards finding a cure, whereas in countries like India the patient groups are struggling even to survive on their own operations. Meeting the operation costs itself is a big challenge.
A Korean SCI delegate insisted on the political nature of what he saw as the maturation process of organisations for people with disabilities, characterised by political struggle and practical perseverance:
It required fighting – chaining ourselves to fences and protest: it’s in our minds – and not dependent on money.
In brief, countries’ institutional, financial and political landscapes greatly affect the kinds of workspaces in which HOs can operate. Clearly, HOs’ workspaces are conditioned not just by their competition, recognition as worthy causes, tax systems and charity by donors but also by political and judicial support and the constraints of the political regimes under which they emerge.
Therefore, although both HOs for MD and SCI support scientific research, the HOs for SCI emphasises the search for cures and health activism in favour of the acceleration of translational research. In terms of political governance, however, political lobbying is feasible mainly in HICs; Chinese delegates considered political lobbying as inappropriate, while in India, delegates maintained, HOs are struggling even to gain state recognition.
Locally Situated Needs and Demands for Treatment
Insight into the needs, treatment, collaboration with industry and knowledge activism of HOs will provide us with a better understanding of the locality- and condition-based needs of HOs. This in turn, will allow us to reflect on how regulatory policies of lobbying FTCM could affect HOs outside the West.
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:
I don’t want to talk badly about India but 95 per cent of the Indian population is economically challenged. Poverty becomes more of a challenge than SCI.
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:
We’ve seen an immense change in the demographics of SCI. Whereas it used to be young active people, like auto traffic accidents and sports injuries, it’s not anymore. In fact, it’s more an aged population. So, we’re seeing people in their 60s and 70s now being admitted for SCI, but I think that’s a consequence of us all living longer and wanting to live independently at home … 50 per cent of SCIs in the UK are non-traumatic so it’s transverse myelitis, tumours in spines. It’s not something that is preventable.
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.
Table 7.1 Locally variable needs for SCI and MD HOs
| LMIC (SCI) | Income support, fair social security and healthcare systems; socio-political awareness, anti-corruption measures Traffic and general safety and affordable mobility devices Combat discrimination of disability/gender |
| HIC (SCI) | Prepare for elderly persons with SCI Legal representation Scientific research |
| LMIC (MD) | Income support and diagnostic facilities Combat discrimination of disability/gender Rehabilitation centres |
| HIC (MD) | Public awareness Facilities in schools Scientific research |
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:
The problem for SCI is that regenerative therapies are not testing function at this point in time; they are safety trials. So, when will we know that they work? We don’t know – it could be 10, 20, 30 years down the road.
An SCI organisation from the UK had also become cynical about the timescale:
I have been with my organisation seventeen years now, and back then I remember it was the first international conference [on olfactory ensheathing cells] and all these scientists from all over the world were saying, ‘the cure is only ten to fifteen years away’. They’re still saying the cure is only ten to fifteen years away.
Persons with SCI in HICs weigh their choices:
There are people in full-time jobs with SCI who cannot afford five, six hours a day to do physiotherapy. That’s just unrealistic. It’s not the real world, and the vast majority of people are saying ‘I’ve got more important things to be getting on with.’
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:
We check papers on the Internet – pubmed – and our CEO has a tight relationship with the Japanese government at a high level, and he has contact with famous professors.
In contrast with other delegates, a Japanese delegate emphasised the trust invested in the Japanese state:
If the Ministry acknowledges a practice … then many patients say, ‘Yeah, you know if Japanese Ministry admits it, I trust it’. So somehow, I feel this trust atmosphere in the government doesn’t mean that the government is trustworthy.
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:
I had met him and he promised to help. I was very excited every day and the Korean government and people were very excited too about how he was wonderful, is wonderful and will always be wonderful, and Korea’s future will be very bright. When a journal showed [his research] to be fake, it was a real disappointment. Some big private hospitals do some research but we cannot trust them. That’s why severe patients go to China or Japan for treatment.
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:
With SCI you suffer many complications, so if you have a pressure sore, can you really stay in the clinical trial? Please, stay healthy and do what you can; be strong on the rehab end, continue to rehab, when you’re out of rehab do something every day to stay healthy so you can participate in a clinical trial and not have the investment in your participation be lost because you come up with a health issue that could have been avoided, that just slows down the whole process.
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 and Knowledge Activism
HOs recommended collaboration with industry, with or without the mediation of the state and universities, as industry would be motivated to market therapies and appliances. But working with industry entails both opportunities and risks. Here, HOs see opportunities for knowledge activism in the form of information gathering and agenda-setting. These activities underpin lobbying with the state for support, protection and adequate regulation.
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:
We work to direct funding to the best research and I mentioned this before. It’s oftentimes not going to the best research. So, we provide the tools to make sure that it gets there through peer-review, and we also try to encourage replication studies.
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.
Table 7.2 Collaboration with industry: Opportunities and risks
| Opportunities | All | Information gathering regarding rehabilitation, clinical trials, new technology, clinical treatment Influence the research, e.g., endpoints clinical trials Accelerate marketing |
| HICs | Get priorities, e.g., translational research, on the research agenda | |
| LMICs | Enhance HOs credibility | |
| Risks | All | Reputation loss when ‘getting into bed with the devil’ Lose the ability to steer research priorities when accepting funding Pressure on patients to get the state to pay for drugs Losing access to treatment after clinical trial |
| Dealing with risks | HICs | Create a strong MOU, legal protection Stick to moral standards Direct funding to the research best for you Involve the regulators Bring stakeholders together yourself Demand replication studies and contributions from universities |
| LMICs | Create an MOU Make HO attractive to company partners Negotiate treatment costs Set up long-term connections with reliable scientists and companies Refrain from collaboration |
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.
Table 7.3 Social, educational and knowledge activities
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.
Conclusion: The Politics of Regulation and the Embodied Identities of HOs in an International Context
One of the meeting’s concluding remarks by a delegate from a HO for SCI sums up a key ideological problem underpinning global activism:
In the end, we [all] have the same possibilities because the older groups can help the younger ones, so if you don’t have some things that we have, for example in Europe, we can help you in having the same rights, the same access and the same conditions in a co-operative way.
A delegate from India reacted:
That’s exactly the catch. The groups in the developed countries can’t help us, because the needs and possibilities are not the same. When they focus on [globally] shared needs of patients, we focus still on our basic needs.
The global dynamics of capitalism privileges some styles of health activism over those of others, showing us that the ‘counter-hegemony’ of the activism in HICs can be hegemonic in itself. Although HOs have needs in common, the historical embedding of HOs show great variety in patient needs and the workspaces that might address them. This is not well reflected in individual human rights–based discourses of international HOs, which, first, tend to exclude discussions on the different priorities of LMICs, who struggle to fulfill grass-root needs; second, insist on the emancipation and independence of patients and the prioritisation of biomedical solutions – lacking awareness of the importance in many communities of the supportive role of the extended family, and of other modes of coping, such as the everyday use of alternative medicine; and, third, tend to be ethnocentric in their advice: for instance, to ‘take responsibility’ through rehabilitation with the aim of clinical trial participation to patients from LMICs may be expensive, dangerous or impossible and the safety and reliability of ‘clinical trials’ and ‘after-care support’ may differ starkly in different parts of the world.
We also saw that there are fundamental differences between the ways in which individuals with SCI and MD embody and identify their conditions socially and politically (Alcoff Reference Alcoff2006; Siebers Reference Siebers2011), to the extent that the former have formed a sense of community, while the latter has not. It seems obvious that, depending on one’s condition, priorities for treatment and care differ and are contingent upon available financial and material support, cultural views about disease, identity and political governance. While persons with SCI often eschew identity politics and aspire to inhabit a ‘normal’ world through quick-fix technologies, people living with chronic conditions may prefer to consolidate their identities of being other-abled. those that embrace their identity as other-abled tend to accept their condition as ‘normal’ to themselves and look for treatment that can improve the lives they lead. Health activism strategies then, are rooted in everyday life conditions, embodied in socio-political identities and shaped by the constraints and possibilities they bring.
This chapter has shown that wealth, where we live and the kind of conditions we suffer shape our views about healthcare needs and the workspaces of HOs, including ‘knowledge activism’, ‘political lobbying’ and ‘collaborating with industry’. In HICs, some influential HOs criticise the bureaucratic slowing down of regulation, its overprotection of ‘free individuals’ and the monopoly of the pharmaceutical industry and its influence over regulation, even where measures are in place to accelerate clinical translation through regulatory clauses and exemptions. For critics, the promise of stem cell research cannot be fulfilled soon enough, so that down-regulation is for them the only way for seriously ill patients to gain access to life-saving treatment. This redemptive pressure to accelerate therapy access is also advocated by international HOs in LMICs, but HOs make clear that their priorities lie elsewhere. But in LMICs, despite the attraction of quick-fix scientific solution, HOs have been suspicious of permissive regulation, which in their view creates uncertainty about the scientific reliability of the therapies available to them. The redemptive effect of down-regulation lies in the belief that it will save lives in a context of ‘strict’ regulation designed to immunise patients from the risks of experimentation. But in HOs in China, India and South Korea, we saw worry about the safety of clinical trials, their efficacy and the fabrication of data; HOs in India were worried about clinical experimentation but also about ‘foreign’ clinical trials that try their luck among the poor when failing to recruit in wealthy countries. At the same time, the growing middle classes in India and China increasingly view stem cell treatment as an opportunity for extending life. They call for reliable regulation. It is important, not just to know which treatments are vetted by ‘international’ standards but to have a reliable compass for gauging the risks and opportunities of ‘as yet’ unauthorised clinical treatments.
Most HOs try to keep a tab on patients that go for ‘experimental medicine’. Decisions to try unauthorised treatment are not just based on hope but also on calculated risk. Ironically, the HOs in LMICs that are hardly recognised by the state expressed the greatest need for official information on the safety of clinical possibilities, while in countries with detailed and transparent regulation, HOs were much more critical of the state. For instance, HOs from the US express little trust that state regulators can fairly balance their ‘rights’ against the interests of large pharma; the European HOs, however, trusted regulators to take their views into account but also criticised them; in India, HO delegates felt that although they were not sufficiently heard by the state regulators, they had to rely on them for information on clinical trials; the Chinese HOs identified with the state; and, the Japanese and South Korean HOs expressed trust in state regulators and emphasised that their voices were heard.
The variety in regulatory trust among the HO delegates partly reflected the political identities of HOs in different parts of the world. And as no global-level regulatory authority exists that can immunise research regulation against violation, patients who can and who can’t afford it are ‘free to choose medicine’ with misleading guidance regarding its potential to heal, provide temporal reprieve or to deliver expensive death. Though, as we saw in Chapter 4, there have been calls for establishing a strong global regulatory authority, it would need to cater for the world’s diversity in health- and regulatory needs. The suitability of regulation within a jurisdiction is contingent upon the material and organisational resources available to HOs in a jurisdiction. And, as we saw in previous chapters, it is the regulatory gaps that have been exploited by entrepreneurs, industry and the state in both HICs and LMICs.
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