Case 1: Informal Forms of Regulatory Brokerage

This first case indicates a basic pattern of opportunistic regulatory brokerage: by taking advantage of regulatory discrepancies, collaboration can give access to a country with less prohibitive regulation.

In Chapter 5, we saw that, despite Japan’s national ten-year project for the development of regenerative medicine, its regulation had been perceived as overly restrictive, slow and bureaucratic (also see Slingby et al. Reference Slingby, Nagao and Akabayashi2004; Nakatsuji Reference Nakatsuji2007). This friction between the stimulation of regenerative medicine and ‘restrictive’ regulation incentivised companies and scientists to go abroad and to collaborate internationally. The Indian–Japanese joint venture, the Z Centre for Regenerative Medicine (ZCRM) is another example of a case in point (Sleeboom-Faulkner and Patra Reference Sleeboom-Faulkner and Patra2011). Its founders boasted a large scientific, political and financial network in both Japan and India and organised clinical stem cell applications for a range of diseases, including spinal cord injury, cardiovascular diseases and cirrhosis of the liver and immune diseases in India. Settled in Japan and established as a cardiac surgeon at a university there, Indian-born scientist-entrepreneur Kumar (pseudonym) commuted between India and Japan to overcome regulatory boundaries. In 2005, Kumar and a group of Japanese scientists and companies set up ZCRM as a charitable company in Chennai, India, with Japanese equity. In 2008, Kumar reported that the company’s charitable goals had led to long-term profit:

Here we find that regulatory brokerage takes place by a simple strategic use of regulatory discrepancy and by avoiding regulatory violation where possible. Although differences in healthcare, wealth and scientific development between the countries played a role, the regulatory discrepancy was crucial to ZCRM’s ability to operate in India.

In India, the Department of Biotechnology (DBT) and the Indian Council of Medical Research (ICMR) had jointly developed ‘Guidelines for Stem Cell Research and Therapy’, enabling scientists to operate internationally (DBT and ICMR 2007), followed by various reforms and amendments (see Chapter 3). In this period, ZCRM avoided the need to apply for formal permission by providing stem cell isolation/expansion services to Indian hospitals (Sleeboom-Faulkner and Patra Reference Sleeboom-Faulkner and Patra2011). This enabled ZCRM to shift the responsibility for the application for permissions to collaborating hospitals. Although India’s IEC/IC guidelines permitted the use of autologous stem cells in research and treatment, protocols had to be approved and registered with the National Apex Committee for Stem Cell Research and Therapy (DBT and ICMR 2007). But, as the Committee did not function well, it opened the way for regulatory tolerance of countless of unauthorised stem cell interventions in hospitals and clinics (Tiwari and Raman Reference Tiwari and Raman2014).

Even after the introduction of the 2013 National Guidelines for Stem Cell Research, which limited permissions to research and was applied mainly by universities and state hospitals, a laissez-faire approach among clinics was tolerated (Tiwari and Desai Reference Tiwari and Desai2018). In Japan, by contrast, similar engagements by reputable universities and companies would have created a scandal. Japan’s style of regulatory boundary-making at the time viewed scientific research in terms of ‘international’ standards for ethics review and scientific applications, despite grumbles about regulation being imported from ‘the West’. This is what gave Japan its regulatory immunity.

Case 2: Regulatory Brokerage with Official Support

A second case shows how international collaborations are brokered using perceived regulatory advantages of the other country as regulatory capital with the support of state institutions.

This opportunistic form of regulatory brokerage is exemplified by the collaboration between KHI and Chulalongkorn University, forged by NEDO. The evasion of Japan’s regulation here needs to be understood in the context of Japan’s scientific and economic long-term political plans to enhance its global competitiveness in the pharmaceutical and medical equipment industries. As discussed in Chapter 6, these plans included new legislation, the ‘Highway for the Realization of regenerative Medicine’, the Japan Revitalisation Strategy and the Plan for the Promotion of Medical Research and Development (Headquarters for Healthcare Policy 2014).

NEDO, a semi-government organisation set up in 1980, was to actively promote the establishment of world-standard technology, as well as its market development. Whilst NEDO originally followed a conservative policy of adjustment to ‘world’ standards, it now adopted a more assertive role of international expansion, supported by a generative annual budget (e.g., 20.8 billion Yen [US$190m; £129m] NEDO 2015). One example of a collaborative network supported by NEDO was the 2012 collaboration described in Chapter 5, between Kawasaki Heavy Industry (KHI) in Japan with Bangkok, where NEDO has an office. KHI, which was developing an automatic cell-processing robot for stem cell applications, wanted to show that marketable products could result from clinical trials using a robotic machine. Despite the strategic policies, it regarded Japan’s regulation, however, as far too slow and restrictive.

NEDO, however, was prepared to help with KHI’s international expansion, even if its international collaboration meant that it violated the spirit of Japan’s regulation. After negotiation with various universities in Thailand, Chulalongkorn University decided to allow KHI’s robotic machine on the premises and to collaborate in a clinical trial. As we saw in Chapter 5, Chulalungkorn University could use the technological support and was conscious that the ‘generosity’ of NEDO and KHI was ‘payment’ for its regulatory capital. The parties signed a memorandum of understanding in June 2012. When asked why, the Thai scientist who had first received the Japanese delegation explained:

KHI strategically chose Chulalongkorn University as a collaborative partner, being confident that it would receive permission for conducting a clinical trial using the robotic machine. Chulalongkorn University, on the other hand, accepted the collaboration because the use of advanced equipment would help it both scientifically and financially. A leading Thai scientist reflected that KHI had been too optimistic about gaining permission for a clinical trial:

Wilipana and colleagues were adamant that what they needed was to build up their regulatory capacity to an ‘international’ level to protect their scientific boundaries and patients. One scientist said that being soft about regulation would tarnish Thailand’s scientific reputation. To what extent this means that the collaboration’s regulatory capital has not paid off is unclear, but it does raise questions about the potential use of Thai patients to prove the processing ability of robotic upscaling, and it prompts questions about the authority of state organisations to evade their own regulation.

Case 3: Brokering Regulation at Home

The next example of active regulatory brokerage in Japan involves the state’s creation of regulatory capital by ‘loosening’ what are perceived as prohibitive regulations in the home jurisdiction. Regulatory capital in such cases involves struggles among interest groups and political brokerage at home. The regulation in this case aimed to get a global competitive edge in regulatory capitalism. To many Japanese scientists engaging in industrial applications of regenerative medicine, it was clear that no industrial stimulation package would work without regulatory reform. Japan, in other words, had to create its own regulatory capital.

The Office of Medical Innovation, a cabinet-level advisory organisation set up in Japan in 2011, played an important role in the development of regulation by reducing sectionalism among the science, health and trade ministries and by bringing industry and science closer together in developing more effective intellectual property and regulatory frameworks in the field. The Japanese Society of Regenerative Medicine (JSRM) and the Forum for Innovative Regenerative Medicine (FIRM) were crucial to directing the development of regulation of the field. In this ‘triple helix’ set-up, involving the collaboration of the government, the state bureaucracy and heavy industry (Johnson Reference Johnson1982; Etzkowitz and Leydesdorff Reference Etzkowitz and Leydesdorff2000), the prominent role of Professor Teruo Okano of Tokyo Women’s Medical University, known for his innovative ‘cell-sheet’ therapy, was key. Made of human cells grown on temperature-responsive sheets, cell-sheet products were used in various clinical applications, including for heart failure, which Okano was intent to market. Professor Okano embodied the triple helix of regulation, science and industry. Being acting-head of the Office of Medical Innovation, president of JSRM, and a co-founder of FIRM, his lobbying with the government was crucial to shaping the regulatory reforms.

The JSRM, established in 2001, had been campaigning for the relaxation of Japanese government regulations concerning studies, clinical trials and clinical applications related to RM. Its 2012 ‘Yokohama Declaration’ made regenerative medicine a priority in the Cabinet Secretariat’s Five-Year Healthcare Innovation Strategy and has been instrumental in the creation of the RMA Act, the PMD Act and the RMP Act, which were approved in 2013 (JSRM Reference Begon, Harper and Townsend2016). Okano’s collaboration with Osaka University Hospital’s cardiovascular surgeon Yoshiki Sawa has been crucial to the success of CellSeed, a company set up by Okano in 2001. In 2007, Sawa announced the successful application of Okano’s cell-sheets into a patient with cardiomyopathy (Sasaki 2012; Okano et al. 2015). Sawa, president of JSRM’s board, led the publication of the Osaka Declaration (17 March 2016), which announced Japan’s role as world leader in universalising regenerative medicine and finding evidence for its safety (JSRM Reference Begon, Harper and Townsend2016). Okano and Sawa were active representatives of the companies they work closely with – CellSeed and Terumo, respectively – and had large networks, including FIRM with its 180+ large member-companies.

In 2013, a well-known leader in regenerative medicine filed complaints about Japan’s regulatory policies, which were widely shared by those interested in the commercialisation of cell products:

Financial inability was not the only factor that stopped scientists from taking their products through clinical trials and working with industry. It was argued that, as Japan did not have experimental spaces or ‘expanded-access related mechanisms’, such as the hospital exemption and compassionate treatment in Europe, or investigational new drugs (INDs) in the US, testing opportunities were particularly limited in Japan. Other scientists and regulators pointed out, however, that Japan’s Medical Practitioners’ Act and Advanced Medical Care gave Japanese PIs similar or more spaces to ‘test’ their products (Tsuyuki et al. Reference Tsuyuki, Yano, Watanabe, Aruga and Yamato2016).

Nevertheless, some leading scientists urged the government to concede the regulatory demands of the Yokohama Declaration. Regenerative medicine needed infrastructural support that the government alone could not supply. Industrial investment was needed for clinical trials in regenerative medicine, but industry was holding off. It was not that the Japanese market was not big enough; it was because infrastructural and regulatory conditions were unfavourable. One scientist explained in November 2013:

According to this scientist, industry is willing to work in a country that ‘builds the platform and provides workable regulatory conditions’: ‘That is why they try the UK first’, he concluded (Hashigawa, 1/11/2013*).

Another reason for regulatory reforms was the Japanese government’s resolve to wean scientists from government funding. Even though its budget for science innovation was only about 10 per cent of that of the US National Institute of Health (NIH) (US$150 billion) (Sonoda, 5/11/2013*), Japan’s government hoped to lower it by attracting venture capital. At the time, the availability of venture capital in Japan was much lower than in the US and Europe (Umemura Reference Umemura2015), and it was hoped that deregulation would get Japanese and foreign companies interested in paying for clinical trials. Down-regulation, it was thought, would make them less costly and would require fewer subjects before any products would be eligible for licensing.

Apart from stimulating industrial investment into Japanese products, the plan was to attract foreign researchers and companies to test their products in Japan in the framework of Japan’s national insurance system. This would, first, strengthen Japan’s ability to organise clinical trials, second, increase the purchase of Japanese products through joint ventures and, third, increase the need for international regulators to recognise Japanese procedures and systems of permission.

As described in Chapter 6, regulatory brokerage at home led to the introduction of a tiered risk system to determine research oversight and enabled expedited marketing approval. Although the government presented the new regulations as a redemptive force, advertising its ability to safely and responsibly expedite the translation of regenerative medicine into clinical therapies for Japan’s ageing population, ministerial discussions of the new regulations emphasised its vision in terms of scientific and economic competition: attracting venture capital, global clinical firsts and the export of health care and regenerative medicine to Asia and beyond.

The regulatory reform created new regulatory capital, altering the relations between Japan and other countries, with Japan’s ‘permissive’ regulation fortifying its global competitiveness. The regulatory system, based on conditional, time-limited marketing authorisation, reduced the safety and efficacy studies required before clinical trials to mainly safety studies and presumptions about efficacy. Nevertheless, speaking of ‘deregulation’ is misleading in some respects. For all the talk among critics about Japan’s ‘deregulation’, the amount of paperwork, checks and registrations involved in applications for permissions actually expanded, not in the least because all of Japan’s stem cell clinics now require registration, and because post-marketing research requirements for high-risk (Class I) time conditionally–approved products had been increased. It was also more than apparent that Japan intended to protect its regulatory immunity, and it did so by providing the world with information of each and every step taken in the clinical trials for Class 1 treatments. Another strategy involved in the protection of its regulatory reputation was the international propagation of its regulatory feats, which is the subject of Case 5.

Case 4: International Regulatory Brokerage

A fourth form of opportunistic regulatory brokerage is also ‘reactive’: regulatory discrepancies that emerge as a result of regulatory downgrading in one country incentivise another country to use the resultant regulatory capital to negotiate new collaborations based on the combination of regulatory assets.

Regulatory brokerage at the level of the Japanese government has laid the regulatory groundwork for expanded international collaborations in the field of regenerative medicine. One political decision related to Japan’s regulatory reforms stipulated the creation of Comprehensive Special Zones for industrialisation in 2013, of which Life Innovation in Keihin Coastal Areas Comprehensive Special Zone for International Competitiveness is one example. It was set up to stimulate innovation in regenerative medicine and cell therapies (Kanagawa Prefecture 2016). These Comprehensive Special Zones play an important role in the facilitation of international collaboration.

Before the promulgation of the PMD Act in November 2014, only two products, J-Tec’s JACE and JACC (autologous cultured cartilage cells for cartilage defects and knee joints) had been approved. Shortly after, two new cell therapy products obtained approval for marketing: Heartsheet, the autologous skeletal myoblast sheets for cardiac regenerative therapy (Terumo Reference Terumo2015) mentioned in Case 3 of this chapter, obtained conditional approval in September 2015, after which Terumo started production in the Keihin Comprehensive Special Zone (Nikkei 2016), and Temcell (formerly Prochymal) – an allogeneic MSC product for graft-vs-host disease prevention was acquired by Mesoblast/JCR Pharmaceuticals (Meldrum 2014) – for which it obtained unconditional approval. Under the new RM Act, all four products were made eligible for Japan’s NIH reimbursement.

The creation of both the Comprehensive Special Zones and the eligibility for reimbursement had been designed to attract international collaborators. And, indeed, the regulatory changes in Japan led to a flurry of purchases and collaborations. Japan’s pharmaceutical and industrial sectors placed regenerative medicine high on their agendas, and industrial groups estimate the domestic market for these therapies could top ¥3 trillion by 2050 (Kahn Reference Kahn2015). Deregulation has made Japan attractive not only to Japan’s pharmaceutical and related industries – some major players include Takeda, Astellas, Sumitomo Dainippon, Fujifilm, Kyowa Kirin, Healios, Terumo and Eisai – but also to foreign companies. Interest in Japan among foreign companies exploded to such extent that one scientist referred to it as kusakariba (草刈場) or ‘cutting from the hay-meadow commons’ (Takeuchi, 5/2/2016*), implying a place from which numerous people hope to profit (for example, RepriCell 2013; Reneus 2014; Cytori 2015; Athersys 2016; Cynata Therapeutics 2016; Densford Reference Densford2016; Pluristem 2016).

Regulatory brokerage has taken on international proportions among wealthy, advanced industrial countries. The negotiations that took place in the Keihin Coastal Area Comprehensive Special Zone in Kanagawa Prefecture illustrate how the particular regulatory features of countries can be combined in international strategies. In this example, Keihin Coastal Areas tries to attract industry, with the support of FIRM. In 2017, ten companies within FIRM (Fujifilm, Astellas Pharma, Janssen Pharma, Regience, Rohto Pharmaceutical, Cell Seed, Wako Pure Chemical, Takara Bio, Tella, MediNet) formed the Regenerative Medicine Industrialization Task Force (RMIT) to establish a development centre for regenerative medicine in Kawasaki, a city central to the Keihin Coastal Area.

In early 2016, I attended the UK-JAPAN Life Innovation Symposium ‘Opportunities for UK-Japan Collaborations in Cell and Gene Therapy’ in Kawasaki. Representatives of Kanagawa/Keihin and the UK’s Cell and Gene Therapy Catapult listed the advantages of their respective science parks in a self-congratulatory dance of mutual grooming. Kanagawa/Keihin is presented as close to Haneda airport, allowing one-day round trips to Asian countries and offering ‘deregulation’, subsidies and tax advantages. Located at a distance from conglomerated areas, it allows for potentially risky R&D activities using blood or bacteria. The local government was introduced as being open to industrial applications in regenerative medicine. Kawasaki’s closeness to Tokyo Metropolitan area, with over 40 million people (‘one-third of Japan’), it was pointed out, makes for attractive access to many patients in a super-ageing society. Conveniently, it is equipped with a Life Innovation Centre (LIC) with a large hospital network counting 15 hospitals and 7,900 beds, and possibilities for integration with other advanced medical technologies. Finally, the Kanagawa Centre for Clinical Research and Strategy boasts PMDA-connections that can facilitate early clinical trial permissions. To reassure the audience of its global status, a number of memoranda of understanding were mentioned, including with Singapore, various states in the US, France, Germany, Finland, the UK and the WHO. The British counterparts showcased a similarly long list of attractions, including the Cell and Gene Therapy Catapult, government support for clinical translation in product development and the incubator in Stevenage.

One prominent British delegate from the regenerative medicine community used the Symposium as a platform for international-level regulatory brokerage: with verve, this delegate recommended the combining of aspects of the Japanese and UK regulatory systems. Identifying a considerable gap between science and patient needs, he proposed the ‘Academia, Business and Clinical approach’, whereby both Japan and the UK score high on government and public support, infrastructure and Research & Development in academia, life-science–industry collaboration, manufacturing, commercial support, cell automation and banking in business and hospitals and translational research in the clinic. However, from a regulatory point of view, the two countries differ: the regulation and reimbursement for cell and gene therapies (CGTs) – a European term for regenerative medical products – in Japan is ‘both sensible and pragmatic’; ‘in the UK it is not’. The key question, he maintained, is:

Typically, the developmental pathway of medicinal products, he explained, is ten to twelve years, but venture capital funds only invest in years five to seven. The financial gap and the risk of no reimbursement by health insurers are the main problems for British industry, he argued. This and Japan’s problem of access to foreign markets could be resolved through a trick: by combining the Japanese and European systems. The problem with current international regulation, the speaker argued, is that it is inappropriate for CGTs:

According to the scientist, the plan involves only two steps:

The ‘trick’ as described above provides a clear case of using regulatory discrepancy as a basis for brokering collaboration to the mutual advantage of both parties.

From the point of view of life scientists knowledgeable about various regulatory systems and aware of the importance of becoming an international player early on, this ‘trick’ is an attractive strategy and conforms entirely to formal regulatory provisions already in place in both countries’ jurisdictions. In this example of regulatory brokerage at an international level, both collaborative partners claim regulatory capital and use this to their own advantage. ‘Their own’ here means to the advantage of industry and researchers, supported by the ministries that support the collaboration. This form of national boundary-making enjoys a high level of regulatory immunity in the home country. It also displays a flexible dose of regulatory tolerance, as it embraces activities that are not covered or vetted by the home-jurisdiction as regulatory strategy. International regulatory brokerage is presented politically as redemptive for patients and industry, while misrecognising the practical realities for patients, who pay for it in the form of taxes, health and valuable time, and scientific researchers who have been forced to reckon with the commodification of science. This misrecognition of patient needs will be discussed further in the context of misrepresentation of the self in Chapter 9.

Case 5: Global Brokerage and Regulatory ‘Harmonisation’

This case of regulatory brokerage shows the importance of the global brokering of new standards for clinical trials and international agreement about regulation to international industry. Regulatory brokerage on this high organisational level bypasses the need to make multiple bilateral deals and can reconfigure the terms upon which regulation is formulated and simplify international negotiation.

Case 4 pointed at some dilemmas related to Japan’s regulatory reforms. Viewed as eroding confidence in scientific standards in regenerative medicine by international critics, including the authoritative International Society for Stem Cell Research (ISSCR) (Daley Reference Daley, Hyun, Apperley, Barker and Benvenisty2016), Japan needed to persuade the world that its regulation was up to the task of safely and effectively testing high-quality regenerative therapy products. Japan’s regulatory efficacy requirements by conditional and time-limited marketing permission differ from those of ISSCR. The ISSCR, an organisation widely (but not necessarily correctly) thought to only represent scientists from ‘Western’ elite laboratories, propagates standards of safety and ethics through its website, members and widely attended conferences. The differences between Japan’s and the ‘international’ (ISSCR) standards entail at least two major interrelated challenges for Japan: first, to prevent damage to the reputation of Japan’s regenerative medicine community, the world needs to be shown that the products licensed without internationally accepted evidence are not inferior when reaching the global market; and, second, to gain access to the global market, Japan needs international acceptance of its cell therapy products licensed in Japan.

To address these challenges, regulators and scientists have tried to gain international acknowledgement of the validity of the new Japanese regulation. They have done this by, first, persuading other governments to follow Japan’s regulatory model, which would turn Japan into a leading example; second, lobbying with global regulatory agencies, industry and scientists to involve them in discussions about regulation; and, third, pushing for international regulatory standards for cell therapy producers.

Regardless of the new ‘deregulation’, many Japanese researchers of regenerative medicine call for clear industrial standards for companies to manufacture therapies that are affordable and safe. This involves the scaling up of production and the creation of international agreement on a ‘smart’ form of cell processing – a form of process monitoring and validation, whereby raw material, process, facility and manufacturing may be variable – which in turn requires scientists to work in tune with the manufacturing process. Regulation resembling ICH guidelines, for instance, would enable the development of therapies attractive to industry. This idea now tops the agenda of the PMDA (Umeda, 27/2/2016*; Hashigawa, 4/3/2016*), and, indeed various stakeholders are working towards this purpose (JSRM 2015: 2–5).

Governmental, professional and industrial organisations – AMED, the PMDA and FIRM – work closely together to promote Japan’s regulatory system abroad and to persuade international industry and regulators of the advantages of its time-conditioned market licensing to both industry and patients. The Stem Cell Evaluation Technology Research Association, a system for the evaluation of marketing and post-marketing founded in 2011, was reorganised in 2015 under AMED and FIRM (SCETRA 2015). AMED, which had a budget of ¥121 billion (US$1.27 billion) in 2014, tasked it with improving the R&D environment. With over 330 staff, AMED negotiates the coordination and insurance of clinical trials and clinical research with Asia (Japan, China and South Korea). It also has established overseas offices in the US (Washington, DC), the UK (London) and Singapore (AMED 2016). Further, the PMDA created the ‘PMDA International Strategic Plan 2015’ to establish a Regulatory Science Centre, and the Asian Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (PMDA 2015). To discuss and propagate Japan’s regulatory system, it regularly invites regulators from other countries to its international conferences (PMDA 2016).

FIRM especially engages with global industry, and according to FIRM Chairman Yuzo Toda, the organisation ‘strives to promote Japan’s novel regulatory system to the world’ (Okano et al. 2015). It also does so in Asia through the Asia Partnership Conference of Regenerative Medicine Associations (QLifePro 2018), the MoHWL’s Japan’s International Pharmaceutical Regulatory Harmonization Strategy (MoHWL 2015) and in the West through the Alliance for Regenerative Medicine (ARM 2016), the main international organisation representing regenerative medicine and advanced therapies in the West. In March 2015, ARM announced its memorandum of understanding with Japan’s FIRM. The Alliance’s chairman, Edward Lanphier said:

With a similar mission to accelerate research, development and commercialisation of regenerative medicine and advanced therapies products, the two organisations seek global regulatory harmonisation.

In short, regulatory brokerage on a global scale formed the extension of the national home-keeping strategy of Japan but was in line with the strategies of global industrial organisations operating along the lines of regulatory capitalism. The pressure on political jurisdictions to vie for competitive regulation may lead them to adjust regulations, which in turn may compromise the regulatory immunity of their jurisdictions.

United States

Various political initiatives in the US have led to regulatory reforms elsewhere in the world. For instance, principles underlying ‘Free to Choose Medicine’ (FTCM), first conceived by a free market policy group, the Illinois-based Heartland Institute (Madden Reference Madden2010: 88) were adopted in Japan’s deregulation of regenerative medicine. As explained in Chapter 7, FTCM maintains that clinical trial sponsors should be allowed to begin selling investigational products to patients on reaching mid-phase II (see Chapter 7). This scheme, which undercuts the need for developing evidence of efficacy prior to sale, found fertile ground in Japan through a Japanese translation (Madden Reference Madden2017), propagating its principles to members of the Japanese government. More widely noted among scientists, however, were the various regulatory exemptions and accelerations provided to medicinal products and biologics in the EU and the US, even though Japan’s regulatory system also afforded ample clinical research through Japan’s Medical Practitioners Act (Tsuyuki et al. Reference Tsuyuki, Yano, Watanabe, Aruga and Yamato2016). And, as discussed below, the South Korean regulatory changes were an important incentive for Japan’s regulatory overhaul.

Some years after Japan’s regulatory reform, the regulatory stances of the US and Japan had been reversed: Japan’s industrial federation FIRM tried to persuade US-based ARM of the merits of its reforms, and the California Institute for Regenerative Medicine (CIRM) hailed the FTCM-inspired Japanese system in its 2016 strategic plan: ‘Thus far the FDA does not appear to have the same commitment and motivation as Japanese regulators’ (CIRM 2015). The same year, the policy group that authored legislation leading to the REGROW-Act proposal, a bill that sought to allow regenerative medicine products onto the US market on completion of a phase II study, also justified the measure by suggesting that ‘Europe and Japan have outpaced the United States in modernising their policies to grant patient access to safe cell therapies’ (Bipartisan Policy 2016). The REGROW bill died in committee, with major opposition from patient movements (see Chapter 9). But new proposals to accelerate approvals for ‘regenerative advanced therapies’ were accepted in an amendment to the 21st Century Cures Act, allowing the introduction of a new FDA regulatory designation for ‘Regenerative Medicine Advanced Therapies.’ The FDA predicted that by 2025 it would be approving ten to twenty new cell and gene therapy products per year (Sipp and Sleeboom-Faulkner Reference Sipp and Sleeboom-Faulkner2019; US-FDA 2019).

South Korea

South Korea was perhaps the first country to give preferential regulatory treatment to stem cell products. In 2011–2012, the Korean Food and Drug Administration (KFDA) (now the Ministry for Food and Drug Safety) issued a flurry of three approvals of the world’s first stem cell–based medical products, adding a fourth in 2014 (Lee et al. Reference Lee, Han, Yoon, Lee and Lee2015). Despite these marketing authorisations, however, none of the products were reimbursed by the Korean NIH due to concerns over the weakness of efficacy data, highlighting a worrisome new role for payers as market gatekeepers of last resort. The Korean approvals attracted criticism for sacrificing quality of clinical data to expedience (Oh Reference Oh2012), as well as envy among researchers in Japan.

Subsequent regulatory reforms in Japan, however, prompted South Korea’s proposal of the ‘chongsaem [translated as ‘cutting-edge regenerative’] law’ to foster the biologics industry. This Advanced Regenerative Medicine and Biopharmaceutical Safety and Support Act was approved in August 2019, and implemented a year later. The law shortened the procedures for drug approval for innovative cell therapies and gene therapies in order to propel their market entry (Lim Reference Lim2020). But the law had become more demanding than initially planned. After an ingredient mix-up scandal involving the gene therapy drug Invossa, developed by Kolon TissueGene, new requirements for long-term follow-up health data on patients during clinical trials to monitor the efficacy and safety of investigational therapies were introduced for already approved drugs. The re-approval of stem cell therapies was required within one year, which meant that Cartistem, Hearticellgram-AMI, and Cupistem required a re-approval based on past clinical trial data (Kim and Kim Reference Kim and Kim2020). Furthermore, healthcare companies, which had formerly collected raw material cells and conducted clinical trials just on the basis of consent from a hospital and patients, now requires approval from the KFDA (Kim and Kim Reference Kim and Kim2020).

These regulatory reforms, I believe, served the need to maintain public and international confidence in the regulation of the biologics industry. Regulatory immunity is essential for South Korea’s jurisdiction to ensure that the government’s sizable investment of 595 billion won ($525.6 million) by 2030 will successfully support the country’s regenerative medicine sector.

Japan

At the time of Shinya Yamanaka’s ‘discovery’ of iPS, Japan had already identified the US as a major competitor in the race to commercialise; its streamlined approval of cell biologics made South Korea a serious contender as well (FIRM 2012). Documents of METI’s policy-making think-tank, the Research Institute of Economy, Trade and Industry (RIETI) reflected this: ‘Though Japan has surpassed South Korea in terms of R&D in the area of regenerative medicine, South Korea has been more successful at commercialization’ (Kurata and Choi Reference Kurata and Choi2012). Further illustrating its concern with regulatory competition, the report further cites the existences of a ‘tremendous regulatory disparities between Japan and other economies’, asserting that ‘the low number of market approvals is caused by the low number of clinical trials’, a deficit the authors attribute to regulatory differences (Kurata and Choi Reference Kurata and Choi2012; Sipp and Sleeboom-Faulkner Reference Sipp and Sleeboom-Faulkner2019).

As explained, the regulatory reforms were incentivised by competition and formulated using principles of freedom and choice. But according to one background narrative to the creation of the RM Act, the regulation had been necessitated by fatalities of patients treated by a Japan-based South Korean biotech company, RNL Bio. (Okura and Matsuyama Reference Okura and Matsuyama2017; PMDA 2017). The JSRM and the PMDA had argued that the unregulated marketing of unproven stem cell–based interventions had turned Japan into a ‘therapeutic haven’ for predatory foreign firms. Thus, the RM Act prescribed the registration of all medical institutions engaged in providing regenerative medicines. Unsurprisingly, the RM Act, though requiring registration of stem cell therapy providers, also created an expanded, now official, market for unsafe providers directed at numerous patients (Sipp and Okano Reference Sipp and Okano2018). This greatly enhanced unsafe provision through the seeming authorisation of registered providers and the reimbursement of their therapies.

As related in Case 5, Japan’s MoHWL has made available funding for outreach programmes aimed at ‘disseminating Japan’s model for regulating regenerative–medicine products, and fostering trust towards Japanese regulatory agencies and get Japan’s regulatory model introduced in other countries’ (also, see Cyranoski Reference Cyranoski2019), while attracting promising collaborations at the same time. One of these collaborations concerns Astro Stem, the world’s first therapy product for Alzheimer’s Disease developed by South Korean company Nature Cell. Fukuoka Trinity Clinic in Japan in March 2018 received conditional permission from Kyushu’s review board for regenerative medicine to offer interested patients Astro Stem (Sohn Reference Sohn2018). The hospital, a partner of the Biostar Research Institute, jointly run by Nature Cell and RBio, the maligned former RNL Bio, started offering their ‘therapeutic products’ in June 2021. It is the presumed regulatory immunity of Japan as a regulatory jurisdiction that now sustained the credibility of these practices. Considering the enormous support and investment by the Japanese population, growing awareness of the ambitious economic and scientific politics behind the reforms might make it hard to recover the trust upon which its regulatory immunity is based.

India

In India, the introduction of the 2017 National Guidelines for Stem Cell Research was an inter-ministerial effort to prevent the immature commercialisation of stem cell products (Lahiry Reference Lahiry, Chaudhury, Sinha and Chatterjee2019) by fortifying the 2013 regulation (ICMR-DBT 2013, 2017). Laboratories involved in research and/or cell therapies using stem cells must have a registered Institutional Committee for Stem Cell Research (IC-SCR), be approved by the National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) and follow GMP and use GLP facilities. Researchers criticised the regulation as expensive and slow, including researchers at Stempeutics, the company that played a main role in the development of the 2013 regulation (see Chapter 3). Even though in 2017 it received conditional approval for manufacturing and marketing of Stempeucel, Stempeutics’ CEO Manohar in 2020 praised Japan’s conditional market approval of stem cell products, under which its Stempeucel can be given to patients in collaboration with the Japanese company Novumcella (Expresspharma 2020).

The 2017 regulation is particularly unpopular with clinical service providers, as it only regulates clinical research applications in the context of clinical trials. Neurogen director, Alok Sharma, urged emulating the REGROW-Act of the US as well as the Japanese and Korean legislations for regenerative medicine to create more permissive regulation for medical practitioners using autologous and minimally manipulated therapies and stricter regulations for cellular therapies sold by corporations as a stem cell product (Sharma et al. Reference Sharma, Gokulchandran, Sane, Badhe and Paranjape2016: 15). But despite the strict guidelines for stem cell research and therapy, the state displayed a blatant regulatory tolerance: India has become a key destination for ‘unproven’ stem cell therapies and was openly criticised by the ISSCR in a letter from its president Sally Temple to the Department of Bio-Technology (DBT) requesting investigation (cf. ISSCR 2017; Tiwari and Desai Reference Tiwari and Desai2018).

In March 2019, following Japan and other countries, India published the New Drugs and Clinical Trial Rules, bringing all ‘more than minimally manipulated’ stem cells as well as stem cell–based products under the Drugs and Cosmetics Act of 1940 (Singh Reference Singh2018). The amended regulation both facilitates clinical trials and clinical service providers. On the one hand, it provides for the combination of phase I and II clinical trials, and it allows conditional approval of cell-based products for unmet needs, if the process or product shows demonstrable safety and efficacy characteristics (Ministry of Health and Family Welfare 2019, cited in Mathen and Sinnappah-Kang Reference Mathen and Sinnappah-Kang2020). On the other hand, clinical service providers of minimally manipulated stem cell-based therapies are able to continue their administration in patients with little oversight. Most clinics in India use autologous stem cells, which require what is controversially called minimal manipulation. Not requiring pre-marketing authorisation, similar classification used by the US FDA allows these unproven stem cell therapies to flourish. Ironically, after India had adopted American-style regulation, regulatory amendments shifted regulation towards Japan’s regulatory regime.

Taiwan

In 2018, Taiwan followed Japan in overhauling strict regulatory conditions by drafting a conditional-approval law for regenerative medicine based on Japan’s legislation. Chen and colleagues from the Taiwan Food and Drugs Administration (Taiwan FDA) and Department of Public Health justified the new design for adaptive licensing, which they had adapted from the PMDA, as follows: ‘Cell Therapy Products (CTPs) may still be developing, and their scientific data may not be sufficient by general regulations. However, for the unmet need of specific patients, CTPs can be used as a therapeutic strategy’ (Chen et al. Reference Chen2017). Tsai and associates described how Japan’s international regulatory lobbying has led to Taiwan being the first jurisdiction to adopt its framework as Special Regulation for Cell Therapy, similar to the Japanese RM Act, which came into force on 6 September 2018 (Tsai et al. Reference Tsai, Ling and Lee2020).

The background story is a redemptive one: a water park explosion in 2015 caused 510 patients to sustain burn injuries. A predicament of skin-shortage was saved by Japanese autologous cell therapy (Matsumura et al. Reference Matsumura, Harunari and Ikeda2016), calling attention to the practical use of stem cell therapy and regulatory change. But in 2013, Japanese and Taiwanese researchers had already co-hosted the Asian Cellular Therapy Organisation (ACTO) to propose the emulation of Japan’s regulatory reform, inviting the Taiwan FDA for this purpose. ACTO’s co-host and founder of the Taiwan Association for Cellular Therapy, Yao-Chan Chen, collaborating with the relevant ministries in both countries, laid the groundwork for this (Tsai et al. Reference Tsai, Ling and Lee2020). By 2020, Taiwan had approved twenty-one cell-based therapy technologies and opened its doors to regenerative medicine companies, such as J-TEC, CellSeed, Hitachi and others in the hope of importing the technology. Nevertheless, mention is made of the confusion among physicians about the effectiveness and liability of the new practice and the difficulties patients have distinguishing the effective cell therapies from others (Tsai et al. Reference Tsai, Ling and Lee2020: 1047).

In brief, Taiwan’s strict regulatory regime followed Japan’s dual-track system with time-conditioned market permission, enabling Taiwan to welcome foreign investment and collaborations.

Mainland China

The Administrative Measures for Clinical Research for Stem Cells (for Trial Implementation) issued in 2015 (CFDA 2015) were to stabilise China’s clinical translation of stem cells. Following Japan, it laid the basis for a dual-track system. On the one hand, pharmaceutical companies can obtain market authorisation for a stem cell therapy from the national Medical Products Administration (NMPA) based on evidence from clinical trials, while, on the other hand, clinical research into stem cell therapies, using GCP and qualified as safe and effective, can be used as technical evidence to support applications for market approval. But the release of the Guidance for Research and Evaluation of Cellular Therapy Products in 2017 (NMPA 2017) and China’s National Health Commission (NHC) draft for comments on the Management of Clinical Research and Transformation Applications for Somatic Cell Therapy (Draft for Comment) (NHC 2019), if implemented, could accelerate patients’ access to cell treatments through clinical applications.

These regulations would extend the dual-track system to ‘somatic cells’. Making a distinction between the phases of ‘clinical research’ and ‘clinical application’, they give hospitals free rein to charge patients for somatic cells as ‘medical practice’ if safety and efficacy are demonstrated through clinical research. According to the system, clinical providers file the applications for permission, managed by the NHC. Unlike the arrangements for stem cell applications, which are subject to more stringent controls, the hospitals carry responsibility for the practice (BIOON 2020; Wu et al. Reference Wu, Wang, Tang, Gao and Huo2020). These drafts were followed by the announcement for data-sharing and the construction of two national stem cell banks in late 2019, and the National Key Research and Development Program ‘Stem Cell and Transformation Research’ in 2020 (Zhihu 2021). Frequent references to the ‘mature regulatory mechanisms in the US, South Korea, Japan, and the EU’ (Zhihu 2021) make clear that impulses for stem cell ‘therapy’ marketing in China are inspired by regulatory competition from abroad. But as shown by the epigraph to this chapter, China nevertheless has to put up with sharp criticism from the ISSCR’s president, Doug Melton (ISSCR 2019).

Foreign investors have been keeping a close eye on this potentially huge market. Although there is a ‘Negative List’ that limits market activities of foreign stem cell investors and providers (Ministry of Commerce 2019], according to the financial-service multinational Deloitte, there is ample evidence that foreign companies can navigate regulation by ‘proactively engaging with the relevant authorities on local registration, collaborating with local companies and institutions and launching optimal clinical programs to ensure maximum speed-to-market in China. In addition, for products already launched in other markets, companies are advised to explore early-access programs to accumulate precious local data and evidence earlier’ (Xie, Wang and Ma Reference Xie and Ma2020: 25). One wonders if this form of indirect regulatory loosening does credit to all the efforts expended on the (Trial) Administrative Measures for Clinical Research for Stem Cells in 2015 (CFDA 2015; Rosemann and Sleeboom-Faulkner Reference Rosemann and Sleeboom-Faulkner2016; Chen 2017; Li et al, Reference Li, Verter, Wang and Ning2019), which was to restore confidence in China’s stem cell science and industry.

United Kingdom

The 2015 report of the Regenerative Medicine Expert Group to the House of Lords already referred to Japan’s progressive Regenerative Medicine Law and maintained that ‘a more innovative approach, informed by experience in other countries such as Japan, would be to develop a system that provides early reimbursement to companies’, including the use of an ‘innovative business model developed between industry, government and the NHS, to support the early adoption of regenerative medicines in the NHS’. This approach would ‘selects therapies for which evidence is limited, but where there is suggestive evidence of significant clinical benefit’ (Regenerative Medicine Expert Group 2015). UK stem cell scientists and companies such as Celixir view Brexit as an opportunity to accelerate the UK’s regulatory pathway (Cyranoski Reference Cyranoski2019: 485). In 2020, the UK’s Medical Research Council (MRC) jumped on the bandwagon in its decision to collaborate with Japan’s AMED by jointly supporting eight new regenerative medicine research partnerships to advance regenerative therapies (UKRI 2020).

State Support for Regenerative Medicine

Policy-makers might consider regenerative medicine to be lucrative and expect it to have a promising future. Economic interest in the field has increased substantially: there has been much trade in the sector and a mounting dedication by governments to support it. According to the Global Regenerative Medicine Market Report – 2019 (GRMMR), the regenerative medicine industry saw venture capital investment expand from $200 million in 2010 to $14.6 billion in 2018, a growth of 7.300 per cent over an eight-year period (ResearchAndMarkets 2019). Subsequent investment, according to Custom Market Insight (CMI 2023) expanded from $14.6 billion in 2018 to $76.04 billion in 2023. Apart from venture capital, the construction of cell and gene therapy manufacturing facilities is undertaken by biotech companies, which are boosting their own production capabilities, as well as by contract development and manufacturing companies (CDMOs) (CMI 2023). The key drivers for the growing market of regenerative medicine, according to GRMMR, are high rates of clinical trials, accelerated pathways for product approvals, new technologies to support cell and gene therapy manufacturing and the potential for cell therapies to revolutionise healthcare.

Most of the initial infrastructural and scientific investment, however, is provided by the state, as industry is risk-averse at the ‘early’ stages of medical product development. Once successful, however, promising start-ups are bought up (Angell Reference Angell1997). A top-ten list of ‘take-over targets’ by the website of GEN (Philippidis Reference Philippidis2018) parades the gems targeted by pharmas. During 2018, for instance, merger and acquisition activity saw large pharma companies make investment in the acquisition of smaller regenerative medicine companies, such as the acquisition of June by Celgene for $9 billion and AveXis by Novartis for $8.7 billion (Hargreaves 2018). In terms of pluripotent cells, the hope is to upscale the production of hESCs and iPSCs using HLA-specific cell banks to create off-the-shelf therapies with genetic correction. Risk-averseness of industry means that scientists try to find ways to persuade governments to invest in upscaling to decrease treatment costs: if they do not, it is argued, only small companies would reap the profit from vulnerable patients (Cossu et al. Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018: 897). Observers, however, warn that, despite the considerable research that has gone into this (Thomas et al. Reference Thomas, Chandra, Hourd and Williams2008; Soares et al. Reference Soares2014), consistent manufacturing is difficult to attain (Pigeau et al. Reference Pigeau, Csaszar and Dulgar-Tulloch2018; Hargreaves Reference Hargreaves2019).

The early stage of experimental therapies using pluripotent stem cells is necessarily expensive, but investment is hoped to be offset by future benefits. Japan’s experience illustrates some key dilemmas faced by countries when joining the race to ‘clinical firsts’. Ironically, the regulatory policies and stimulation packages of the sector require the population – who pays part of it – to be extremely patient, trusting and tolerant. Nobel Laureate Shinya Yamanaka has frequently warned that the stage of developing human-iPS and ES-cells could take over thirty years, asking the Japanese population to support iPS for the long haul. The first iPS clinical trials in 2014, using $900,000 to develop and test the iPSCs, showed that iPSCs could improve the sight of a woman with AMD, but Yamanaka made clear that ‘Regenerative medicine is not going to cure patients in the way they hope’, as the cells did not reverse the condition (Normile Reference Normile2017). In 2020, Yamanaka wrote how, over twenty years, scientists have been fighting against the practical challenges of tumorigenicity, immunogenicity and heterogenicity, even though the field shows immense promise with clinical therapies reaching clinical trials (Yamanaka Reference Yamanaka2020). Confidence in the future of iPS among Japanese citizens has been very strong, but for how long will they be prepared to wait and bear the cost? Why do governments continue to invest?

Competitive Desire in Governments

Without competitive desire, politicians are not likely to put their money on the horse of regenerative medicine: beating other countries to a clinical first block-buster in regenerative medicine could mean fame, profit and even economic growth. Japan’s regulatory and investment policies for the life sciences, as we saw in Chapter 8, were soon followed by other countries, propelling forward the race to successful clinical applications. The competitive desire to gain an edge over rivals can be easily spotted in political discourses on science, their overhyped language often seems contradictory. Declaring Japan as world leader in regenerative medicine research, in 2012, Japanese Prime Minister Shinzo Abe promised to invest ¥110 billion (US$1 billion) and announced regulation that would accelerate the translation of iPSCs into clinical applications (Cyranosky Reference Cyranoski2019). Countries that want to be world leaders in regenerative medicine broker their regulation, provide financial facilities and create national expectations of success. But decision-making based on competitive desire is not confined to political strategies isolated from science and industry. References to world leadership, competitors in the field and requests for crucial investments and ‘not over-rigorous’ regulation to facilitate translational science constitute common parlance prevalent among scientists and regulators when considering funding. Examples from the House of Lords, UK, debating the regulation of regenerative medicine in 2013 illustrate this (House of Lords 2013: 11–15, italics are mine):

• Sir John Tooke: We do not want over-rigorous regulation where it is not required because a trial is, for example, of very low risk. On the other hand, the area that we are discussing this morning is at the sharp end of medicine where some of the risks are unknown and many of them are more considerable than the application of a conventional small-molecule pharmaceutical product. So, in the rush to get regenerative medicine into practice and into commercial exploitation, we must be aware of some of the risks that are present.

• Professor Robin Ali: We are leading here, yet we have not yet built up in the UK the leading infrastructure [for gene therapy] to be able to go on to the next phase, to capitalise on the proof of principle and to capitalise really on technologies and the clinical trials that have been done in the UK, because there has not been the long-term investment on a scale required to allow us to expand. We see that in the US: many institutions there have invested. France, too, there are big facilities for GMP manufacture of vectors. These countries are in a much better situation now to really expand and capitalise on the UK’s success.

• Lord Willis of Knaresborough: My question is really to Professor Tooke. There is an issue that comes to us every time we talk to researchers on the ground, which is really about regulation. Professor Ali quite rightly said that having strong regulation is what makes us very effective in the long-run but going through that morass of regulation is hugely difficult. Indeed, it will get worse because European directives in particular, and some of the court judgements in Europe will create new problems.

• Lord Patel: My interest is that we do not miss out, as we have done previously – for example, in monoclonal antibodies or in gene therapy – in regenerative medicine translation research, so that when the science is ready to be translated, we have all that is necessary in place to do the translation and we are not caught out by other countries such as France, the United States and maybe even Japan and others being better at identifying what would be required and putting it in place so that they jump the gun in translation ….

It is not unusual for scientists and regulators to compare themselves with neighbouring and rivalling countries, forever lobbying for better infrastructures, the ‘right’ regulation and the appropriate investment for aspiring world leaders. Competitive desire underpins not just the acceleration of regulatory permissions and clinical trials but also the race itself. To many scientists and observers, academic competition is crucial for the healthy development of science (Merton Reference Merton1957; Collins Reference Collins1968), even if scientists dislike it themselves (Hagstrom Reference Hagstrom1974). But competitive desire inevitably ties in academic competition with the economic and international dimensions of competition; it threatens to leave behind the value of science in a rat-race for funding, clinical firsts, patents, publications and national ambition (Martinson et al. Reference Martinson, Crain, Anderson and De Vries2009; Fanelli Reference Fanelli2010; Ioannidis Reference Ioannidis2011; Fang et al. 2015; Smith Reference Smith2021), while it is exactly in the absence of competition that transformative discoveries often occur (Fang et al. 2015).

This we saw illustrated in Japan, where the realisation of high hopes requires long-term commitment and considerable investment of social and financial resources, at the expense of resources previously earmarked for other fields (Chapter 6). Apart from eating into the budget of basic science in the life sciences, investment into other areas of innovation, such as tissue engineering (e.g., scaffolds) and physiotherapy (e.g., older osteoporosis patients benefit more from physiotherapy than from stem cell injections [Iijima et al. Reference Iijima, Isho, Kuroki, Takahashi and Aoyama2018]), were at stake. Most governments are unable to sustain the large investments associated with regenerative medicine, especially when it comes to full-blown clinical research trials. Though governments sometimes co-finance clinical trials (see Hauskeller Reference Hauskeller2018), in the long-run, they have to rely on industrial investment. To make clinical trials more affordable and less onerous, scientists have argued for alternative forms of regulation (see Chapter 2). In Japan, the regulatory overhaul and the efforts invested into science-industry collaboration through AMED, indeed, led to an explosion of industrial investment. Here, the introduction of the PMD Act played a crucial role in forging the trust invested by industry in the government’s commitment to continue investing in regenerative medicine.

More than ever, resources are concentrated on translational rather than on basic research, while scientific collaboration with industry changed the dynamic of academic research at the universities, which according to researchers has become plagued by administration, management, regulation, competition and secrecy (Chapter 6; also, see McCain Reference McCain1991). While academic research is being usurped by industry, regulatory facilitation made clinical trials more affordable. Industrial investment, however, usually aims at patents and royalties, making treatment costly and yielding little immediate health gain. For this reason, the Japanese government negotiated reimbursement with national insurance companies to cover the expenses for therapies under development (Chapter 6): This move shifted payments for scientific experimental research to taxpayers and patients, the enablers of the development of future therapies. The brunt of the costs involved in competitive desire is carried by those who have little knowledge of its existence.

The Clinical Promise of Regenerative Medicine

Japan’s experience is repeated in competitor countries. Government investments into therapeutic promise and scientific ambition raise public expectations and appeal to the public for support, forbearance and generosity. It is no wonder that, as we saw in Chapter 7, many health organisations (HOs) place high hopes on regenerative medicine and are keen to work with industry, while at the same time they harbour suspicion, doubt and scepticism of its success. Considering the great investment into infrastructures, clinical trials and commercialisation, the adjustment of regulations, the high expectations of clinical applications and considerable public sacrifice, an important ethical question is whether regenerative medicine does what it promises: do the financial and regulatory investments justify returns in terms of patient health and high-quality science? A more pertinent question here is whether the answer to this question is of any relevance to the competitive desire that drives the investments in the first place.

Responses to the first question are ambiguous: according to Cossu et al. (Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018), results in terms of therapies in the field of regenerative medicine vary from clinical efficacy for previously incurable and devastating diseases to, more usually, modest or no effect. Competition in what are internationally accepted as legitimate clinical trials is afforded mainly by HICs, and their research outcomes have highly uncertain routes to the market. Competitive desire also infects scarce-resourced LMICs, and, hence, thousands of research projects are conducted in medical schools and commercial clinics around the world. But there is little evidence that regenerative medicine can address polygenic and acquired, that is, most, disease conditions any time soon (Cossu et al. Reference Cossu, Fears, Griffin and Ter Meulen2020). At best, in their drawn-out experimental stage, even with safety measures, regenerative therapies expose patients to risk, as outcomes are hard to predict. Though life scientists see great potential for regenerative medicine to reduce suffering and to lower heath spending for increasingly widespread conditions, such as heart failure (Lesyuk et al. Reference Lesyuk, Kriza and Kolominsky-Rabas2018), the realisation of these ‘estimations’ have been expected for decades.

For governments’ public health policies, the cost-effectiveness of treatment is a crucial factor in deciding to fund the development of regenerative medicine for medical purposes at home. Although the ability to tackle widespread conditions through regenerative medicine, such as heart disease, diabetes, stroke, Parkinson’s disease and spinal cord injury, would save millions in healthcare and social care in the long run, the costs of regenerative medicine are high and would have to be paid at the time of treatment. In HICs, the costs associated with regenerative therapy are likely to be borne by the health services, but currently only a handful of rare diseases have been successfully treated (Cossu et al. Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018). As we saw in Chapter 7, efforts to accelerate the development of regenerative therapies, though supported by some HOs and their governments, are not welcomed by all. Some HOs actively oppose the brokerage of down-regulation. For example, in the US, a group of ten health organisations, including the National Organization for Rare Disorders (NORD) and the Michael J. Fox Foundation for Parkinson’s Research (MJFF), opposed a bipartisan bill that would let FDA grant five-year conditional approval of regenerative medicine products. The organisations worried that the bill would compromise patient safety and that it would be difficult for the FDA to withdraw products that receive the conditional approval under the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act (Wilson Reference Wilson2016). The case shows that that some regulation does not inspire confidence, even among the patients that advocate the clinical translation of regenerative medicine.

Academic studies make much of the great cost-effective potential for chronic and life-limiting illnesses such as DMD or Crohn’s disease, with high, recurring costs of care and low health-related quality of life. We already saw in Chapter 7 that many HOs for DMD do not prioritise regenerative medicine. Many people with DMD are not prepared to spend their lives commuting to hospitals to submit themselves to the medical regimes of clinical trials on the off-chance that they improve their condition; many do not desire to become ‘normal’ (Kato and Sleeboom-Faulkner Reference Kato and Sleeboom-Faulkner2018). Nevertheless, numerous studies that calculate the costs of disease advise funding bodies on the development of therapies on the basis of forms of cost-benefit analysis that take little notice of what health improvement actually means to the patients themselves (e.g. Landfeldt et al. Reference Landfeldt, Lindgren, Bell, Schmitt, Guglieri, Straub, Lochmüller and Bushby2014). When governments decide to support the development of regenerative treatment for DMD with an eye on saving costs, in terms of national insurance, this would still require a huge amount of upfront investment, which would be unaffordable in most countries.

Crohn’s disease (CD) is an example of a condition that has become the target of regenerative-therapy hyping, using phrases such as ‘giving patients a new immune system’ and ‘radically changing the course of the disease’ (see Queen Mary University of London 2018). Early trials of stem cell interventions in CD have had mixed results, with some short-term successes but also a significant incidence of side effects, including the death of one patient (Queen Mary University of London 2018). Research into the decision-making and expectations of people with severe CD to have autologous haematopoietic stem cell treatment (Cooper et al. Reference Cooper, Blake and Lindsay2017) indicates that decisions are influenced by participants’ histories of battling with their condition, a frequent willingness to consider novel treatment options despite considerable risks (also see Lindsay et al. Reference Lindsay, Allez, Clark, Labopin and Ricart2017; Qiu et al. Reference Qiu, Feng, Chen, Liu and Zhang2017) and, in some cases, a high expectation of the benefits of trial participation influence the decision to join a clinical trial. Not surprisingly, potential therapeutic mis-estimations occur, whereby the research participant underestimates risk, overestimates benefits or both (Cooper et al. Reference Cooper, Blake and Lindsay2017). Partly, this is due to the difficulty for patients to recognise that clinical trials are not just about trying to improve patient conditions but also about acquiring scientific knowledge and sharing them in publications (Cooper et al. Reference Cooper, Blake and Lindsay2017). Similar to what we saw in Chapter 7 in relation to treatment priorities, this indicates among HOs for DMD and SCI, the process of decision-making about having treatment is shaped by the physical, socio-economic, cultural and relational aspects of a person’s life.

All in all, government decision-making around regenerative medicine based on cost-benefit analysis and clinical outcomes is not straightforward. First, it makes false assumptions about what are costs and what are benefits. The costs do not just constitute those of financial investment but include harm related to the process of developing experimental medicine such as unknown side-effects, the investment of false hopes, spending time on commuting to hospitals and the medical regimes imposed on patients when undergoing a clinical trial. Second, people living with a condition may develop an identity associated with the lifestyle afforded by it. Many accept and like their identity, and do not desire or are not able to become what goes as ‘normal’ (Kato and Sleeboom-Faulkner Reference Kato and Sleeboom-Faulkner2018; Chapter 7). Third, the effort invested into regenerative medicine closes the doors for other medical research. This ‘inverse care law’, which favours distributional analysis of scarce healthcare resources (Cookson et al. Reference Cookson, Doran, Asaria, Gupta and Parra Mujica2021), is put strongly by Cossu et al. (Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018): ‘If policy-makers do opt for high-risk, expensive, but potentially revolutionary regenerative therapies with some tangible effects, they need to balance this against foregoing other, perhaps less-ground-breaking, cheaper research options with tangible effects for the wider population of patients.’ And, lastly, even if regenerative medicine can alleviate a number of conditions, we do not know if its production will be feasible and affordable, as this involves questions of upscaling. The long-term effects of upscaling on the body and individual therapies of the live cells on the body may necessitate research over generations, before we know its ‘full’ biological ‘costs’ and ‘benefits’.

Lowering the regulatory thresholds to accelerate clinical research in regenerative medicine involves risks and substantial costs. But it is doubtful that costs and benefits of medicine and health can be expressed adequately in financial terms. Patient experiences and decision-making indicate controversy about what is needed, depending on the condition in question, means and socio-cultural environment. It is an open question as to whether regenerative medicine can address widespread conditions cheaply, and where investments should be drawn from traditional scientific approaches, especially in countries with scarce resources. In fact, it is doubtful that governments can easily redirect funding. Because past investments are too large to fail, some might deem it necessary to change the ‘social contract’ between regenerative medicine and the public, as discussed by Cossu et al. (Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018).

Social Contracts

The social contract upon which basis medical progress is made, the social license by which scientists are permitted to conduct research, according to Cossu et al. (Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018: 904), needs to change so as to involve the public in the development of regenerative medicine: ‘The social licence [between scientists and public] is more passive than the arrangement that is needed if cell and gene therapy is to be harnessed for mainstream use’ (Cossu et al. Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018). Although researchers risk losing their license to conduct research if they do not follow regulatory guidelines, such as applying for permissions and following regulation, Cosu et al. argue, few expectations are made of the public. In this context, other ethicists have argued that the public has a moral obligation/duty to participate in clinical trials, because everyone would benefit from scientific research (Harris Reference Harris2005; Chan and Harris Reference Chan and Harris2009). Cossu et al. refrain from going this far but instead argue that a good governance framework would increase ‘the sense of mutuality between the public and scientists’ and also enhance ‘the sense of a common project that will take time to come to fruition’. But by not taking into account the intimate ties of science with the state and industry in specific (Guston Reference Guston2000), and regulatory capitalism in general, I argue that this proposal overestimates its ability to cultivate a sense of mutuality that is meaningful.

The proposed social contract involves efforts from both scientists (competence, openness, acknowledging and addressing concerns, transparency, trustworthiness, providing accurate information) and targeted patient engagement and publicity initiatives. Although the desired qualities in scientists are commendable, they are clearly not new and they do not address issues of disagreement on the use of cell therapies, the affordance of particular forms of governance, the secrecy entailed in competition and working with industry and the aversion to public scandal. It is not difficult to see how a social contract based on engagement with the public, as has been the case in Japan (see Chapter 6), can motivate patients to queue up for participation in clinical trials and support a multi-decade project. While Japan’s RMP Act since 2014 guarantees researchers and industry the means and availability of patients to achieve regenerative medicine, taxpayers and patients foot the bill and expectations had to be vastly downscaled. It is clear that acquiring public support is in the interest of innovative scientific undertakings. As political scientist Brian Salter (Reference Salter2007) pointed out, if public support is gained for a particular scientific field then the authenticity of the future market becomes more tangible; and if translated into political support, then the winning of scarce scientific resources becomes more likely. To be politically effective, Salter concludes, advocates must be seen to act responsibly, rationally and with due discretion, that is, to conform to the values advocated above.

Apart from the question of its use as political strategy, there are various interlinked issues that arise when requiring the public to actively engage in regenerative medicine as a part of the social contract between science and public. First, for public engagement with and participation in science to be of value to a democratic consultancy, that is, as a tool of democratic decision-making about scientific development, it must not be a way to subject it to a particular scientific project through which it can come to harm. This is why it is important to know who benefits from support to a particular project in the first place (Leach et al. Reference Leach, Scoones and Wynne2005). This brings us to the second issue of why a particular scientific project is privileged: it is not clear whose interests are served by the social contract proposed by Cossu et al. (Reference Cossu, Birchall, Brown, De Coppi and Culme-Seymour2018). Although more mutuality between scientists and public may be desirable, ‘mutuality’ implies a different kind of power relation compared to the dependence relation inherent to ‘patient engagement’ and ‘patient participation’ that are envisaged by Cossu et al. Furthermore, the proposed social contract does not consider the direction in which science is developing: as we saw above, the focus on regenerative medicine is driven not just by concerns for particular medical health issues but also by profit, career and other motives linked to competitive desire. It is not clear to what extent regenerative medicine is a desirable solution to the conditions on its target lists (Chapter 7).

A third issue is whether a social contract can have predictable effects in the global context of regulatory capitalism with its endemic practices of brokering regulation for endings that have little regard for social contracts. Under global capitalism, investment into science digs wherever it can satisfy a future market, rather than where urgent problems are to be resolved (Busch Reference Busch2000). Scientists, responsible for the scientific aspects of their work, should not also be the regulators of their work, especially not when they are in economic, political and cultural competition with scientists in other jurisdictions. In other words, the proposed social contract ignores the important fact that regulation in the current world, the main mechanism for protecting patients (and scientific development) against uncontrolled experimentation, leads a socio-political life of its own – both nationally and globally.

Competitive Desire and the Sacrificeable

In market economies, transactions involve a distancing mechanism that leaves the seller and buyers free of any ties of duty: you pay and you receive – that is it. This core feature of market economies based on competitive desire contrasts with the ongoing, circular relations of exchanges, which are subject to the social contracts of gift economies (Anspach Reference Anspach2017). Gift economies are far more relational compared to market economies and include a range of social codes that ensure socio-political continuity. But they can be plagued by upheaval, in particular as a result of the obligation to retaliate mis-behaviour or to make sacrifices to end violent cycles of revenge (Girard Reference Girard1986). Philosopher Paul Dumouchel argued in this context that market economies universalise the category of ‘sacrificeable’ victims (Demouchel Reference Demouchel2015) but on a larger scale: not just among those who risk their mental and physical health in the course of their employment but also among those who suffer from conditions and are wanted for experimental research. The victims are those whose (mal)-treatment, death or bankruptcy will not result in vengeance. It is well-nigh impossible to know whether severely ill patients die as a result of ‘immature’ treatment, and those that pay their life-savings for non-effective or maleficent interventions usually do not have recourse to justice. Who is in a position to blame the state for its regulatory facilitation of innovative treatments? Who can sue a clinic that raised unrealistic hopes but gave no guarantees? What are unrealistic hopes?

Even when accompanied by a list of ethical conditions, ethics review and systems of supervisory control, the strengthening of the social contract between scientists and public/patients may have dire consequences: not taking into account the impact from the capitalist market, international competition and regulatory practices exposes ‘the public’, that is, ‘patients’ and ‘volunteers’ to the risk of being sacrificed at the altar of the progress of regenerative medicine. Despite the authority of international stem cell organisations, such as the ISSCR and the ISCT and the publication of research ethics on their websites (ISCT 2015; ISSCR 2016), the international arena of regenerative medicine is not likely to adhere to their guidelines. Similar to tribal gift economies, the global space of regenerative medicine is characterised by the absence of an overarching state (Blanc and Bessière Reference Blanc and Bessière2001; Anspach Reference Anspach2017): there is no transcendental authority. In societies dominated by gift exchange, sometimes transactions occur with foreigners that are similar to market exchange: without mutual obligations. As put by Anspach, ‘in such transactions, one has the right to cheat, steal, or wage war’ (Blanc and Bessière Reference Blanc and Bessière2001).

Similar frictions between local social contracts and deals with ‘outsiders’ occur in regenerative medicine. There are practical limitations to a social contract of a public engaged with the clinical trials needed for the translation of regenerative medicine in a global context of regulatory capitalism. The market mechanisms that necessitate a social contract between public and science cannot be easily controlled where national healthcare systems become part of industrial projects with global interests. The consideration of proposals for public engagement with regenerative medicine has to take into account the friction between global competition and the local investment of tax money into clinical trials, of which physical risks and hopes are shouldered by research participants. This has implications for how the social contract between science and public would work in practice.

Clinical Trials and Access to Patient Populations

The reign of regulatory capitalism raises the question of whether public engagement between science and patients leads to a co-optation of the latter into clinical research trials and, if so, on what basis. Currently, populations and patients are a lucrative subject of data collection for clinical trials. Clinical trials are popular among populations with scant healthcare access, the elderly population of ageing societies and patients that have run out of available options for treatment (Gwanade Reference Gawande2015; Haslam Reference Haslam2022). Under conditions of global competition, the knowledge of regulatory infrastructures and patient pools are important to clinical researchers, the organisers of clinical trials, as well as to highly profitable Clinical Research Organisations (CROs) (Petryna Reference Petryna2007; Montgomery Reference Montgomery2012; Sleeboom-Faulkner Reference Sleeboom-Faulkner2016). Conversations with dozens of stem cell scientists from Asia and Europe indicate a range of factors that play a role in determining where research trials are located and in deciding which disease conditions to target (see Chapter 5 and 7). These factors relate to the profiles of research and health infrastructures, disease populations and to their socio-economic environment. Knowledge of research infrastructures and research populations is crucial to the quality of research and to estimating profit margins. Important infrastructural criteria include local regulatory requirements; the time and costs of obtaining research and marketing permissions; access to research funding; the availability of medical, linguistic, scientific and technical expertise; the reputation of collaborating research and medical institutions; the certification of laboratories and clinics and the sensitivity of the local media to stem cell provision and public attitudes (Sleeboom-Faulkner Reference Sleeboom-Faulkner2016).

The socio-economic environment and attitudes towards clinical trials of potential patient populations are just as important. Thus, to optimise research conditions, the organisers of multi-centre stem cell RCTs may look for a locality with a particular patient pool positively oriented towards and expedient to clinical research. To optimise standard treatment, trial participants may need to be precisely instructed about procedures, drug regime, sanitary conditions and other necessities to render the clinical trial scientifically sound. This requires participants to understand the language in which they are instructed, enough knowledge of what clinical interventions are for, to adopt alien cultures of hygiene and diet, to be free for the duration of the treatment and to be able to afford the expenses associated with insurance, transport, and time off work or away from home (Sleeboom-Faulkner Reference Sleeboom-Faulkner2016). If particular conditions do not meet the scientific protocol of an RCT, the organisers may try to control or cancel out deviations of participating local patients by altering the conditions and habits of research participants to suit the needs of the trial. Thus, diets, housing and exercise regimes may have to be adjusted (Rothwell 2005; Will Reference Will2007; Geissler et al. 2008: 705; Montgomery Reference Montgomery2012).

Features of populations and local conditions can also be internalised into an RCT. This is important as the efficacy of some clinical interventions are sensitive to socio-environmental conditions, such as poverty and pollution. Thus, research participants bring into the experiment their particular social conditions, many of which may be related to healthcare, gender, age, diet, medicine, hygiene and attitudes, which shape the reaction of the experimental body, and which may influence the development of the experiment and its results. The internalisation of undesired local traits and conditions may be unpreventable and can bias the experiment (Montgomery Reference Montgomery2012). The internalisation of local conditions and traits, however, can make scientific sense in ‘pragmatic trial’ designs, for instance, when ethnic background, age, gender and environment are closely monitored and measured. Thus ‘race’ may be hypothesised to be sensitive to certain chemical components in drugs. However, if a particular population is known to lack healthcare access, such population could also become the target of patient recruitment for reasons of accessibility (Duster 2005; McCain Reference McCain2005). Depending on the particular research design and aims, knowledge of the public can be manipulated for scientific and for exploitative reasons (Sleeboom-Faulkner Reference Sleeboom-Faulkner2016). We saw in Chapter 5, for instance, that collaborating with scientists in Thailand was attractive for its large patient pool, limited healthcare resources, relatively cheap scientific expertise, the country’s attractive regulation and in need of expensive equipment.

Certain aspects of a population’s conditions, then, are internalised into the trial design, not because they are expected to contribute to state-of-the-art research or to benefit patients but because other interests are at play, such as market-share, patentability and profit. Similarly, social knowledge about patients can also be important to decisions to collaborate or to locate therapy provision centres, including healthcare access, insurance, education, religious belief, wealth, living conditions and family situation, which may all be valuable for patient recruitment purposes (Patra and Sleeboom-Faulkner Reference Patra and Sleeboom-Faulkner2009; Sleeboom-Faulkner and Patra Reference Sleeboom-Faulkner and Patra2011; Sleeboom-Faulkner Reference Sleeboom-Faulkner2013). Furthermore, knowledge of a country’s healthcare system, regulation, patient pool, communication system, expertise, jurisprudence, insurance system and science policy can be expedient to stem cell enterprises and CROs conducting RCTs (Angell 2004; Rajan 2006; Fisher Reference Fisher2009; Petryna Reference Petryna2009; Dumit Reference Dumit, Good, Fischer, Willen and DelVecchio Good2012). The question is whether a social contract between science and public will be compromised by the pressures of competition and the race for clinical firsts.

In short, uncertainties about the aims of the social contracts between the public and scientific institutions and the unpredictability national and international political and financial pressures under regulatory capitalism make it necessary to take into account the possibility that knowledge, rather than utilised to serve the needs of patient health under agreed regulation, becomes commodification and sold to be used for commercial purposes under different regulatory arrangements. As under regulatory capitalism, patients are objectified as pools and scientific knowledge is commodified as assets, any social contract between science and public should be understood in the particular context of the community in which it evolves and through the wider pressures it is subject to.

Creative Desire

Under regulatory capitalism, thinking in terms of national competition requires strategies that involve the objectification of other countries and the creation of the distance between peoples through comparison, it presupposes a rational individualism that relegates love, ethics and solidarity to the realms of the naïve, the sacred and idealism. Hard-nosed decision-makers usually do not like to be associated with these. Taking inspiration from Rebecca Adams’ work on ‘creative mimesis’ and ‘loving desire’ (Adams Reference Adams and Swartley2000), however, it becomes possible to see, not just why competitive desire does not have to underlie all economic exchanges but also how a constructive, loving form of desire can serve as a fundamental generative principle of what I call ‘caring solidarity’, if rooted in local notions of wisdom and includes the virtues of prudence and social justice (explained in the section below).

Creative and loving forms of desire, like competitive desire, are generative, mimetic principles. Creative desire accounts for constructive, non-violent symbolic and material exchanges that form the basis for communities. Competitive desire, a principle that mimics and generates selfish behaviour based on envy, dominates creative desire in a world characterised by regulatory capitalism. In a world of regulatory capitalism, competitive desire can only temporarily be superseded by means of the law and regulations in a community, because international strife puts pressures on nation-states to adjust to the global dynamics of competitive desire. The damaging effects of competitive desire go beyond those of the escalation of regulatory violence. It affects the ways in which countries self-define as ‘backward’ or ‘developed’ and influences the political priority setting in matters of science and healthcare (Chapter 2). Viewing themselves through the eyes of the powerful, Othering leads to self-objectification and emulation. Therefore, scapegoating, competition and mimetic desire are more generative than realised at first glance: we are not just dealing with sporadic violations of regulations. Rather, we are confronted with systematic and strategic internalisation of regulatory conditions that not only puts some groups at a disadvantage and scapegoats them but also places them in a position in which mimesis leads people to objectify and misrepresent themselves. From this vantage point, the only way forward may seem to be the emulation of the ‘successful’ strategies of what are viewed as the more ‘developed’ countries.

A more constructive form of desire from a non-victimised perspective would avoid that victims identify with the victim position. It is the objectification of others rather than ‘acquisitive imitation’ (Girard Reference Girard2016) that is the locus of violence in competitive desire. Following Adams in her revision of Girard’s ‘imitative desire’, I suggest that powerful HICs address their health needs on the basis of ‘caring solidarity’: as we saw in Chapter 7, rather than imitating and vying for the biomedical aims and regulations of other communities, resources are better spent when matched with the aims of and health needs embedded in the livelihoods of their local communities. As we saw in Chapter 7, the medical challenges of HOs for DMD in India, Japan, Europe and the US are quite different.

The health needs of LMICs and/or less powerful communities, rather than adopting the health models of wealthy countries, may be more appropriately fulfilled according to local conditions and local aims. Only when regulatory conditions and biomedical solutions correspond to the means and livelihoods of local communities can they begin to realise the desires engendered by their cultural subjectivities rooted in local creativity, including their views, values, sensory perceptions and ways of living. A shift in thinking in terms of ‘society’ to ‘community’ could draw attention to the relational nature of healthcare.

The notion of community draws attention to the importance of meaningful relations regarding materials wealth. By only desiring the subjective integrity of the self-conception of others, rather than desiring their objects (that is, the paraphernalia of power, wealth and status), communities are able to acquire greater well-being and improve the relationality within and between communities. Only then, the subjective integrity of other communities, unlike objectified Others and their objects, are not envied and appropriated but valued as integrated modes of living. It may be objected that creative desire implies that material exchanges are not stimulated and regulated, possibly leading to isolated communities and clandestine and exploitative exchanges. But, as argued above, creative desire is a generative, mimetic principle: it can be understood most fruitfully in the wider context of mutually beneficial cycles of gift-giving and solidarity. This discussion, which underpins the vision of caring solidarity, I will pick up after introducing the considerations of prudence and justice.

The Considerations of Prudence and Justice to the Common Good

The prudence with which communities develop innovative health products and the fairness and equitability of the distribution of healthcare resources are crucial considerations to the acceptability of medicine to communities. I speak of considerations here, because the practices in which the notions of ‘prudence’ and ‘justice’ acquire their meanings vary; communities deliberate, attend and understand prudence and justice differently. I use these considerations as a heuristic way to think about what kind of medicine might serve local communities appropriately: how can communities invest into healthcare in a way that (a) avoids regulatory violence; (b) includes patient groups that are not best served by the promised fruits of regenerative medicine; (c) is embedded in the socio-cultural lives of national and local communities, including non-human life, and (d) is morally bound to undertake action to accommodate differences between the abilities of people in need through mutuality and relations of care.

The considerations of justice and prudence are relevant, first, to determine the conditions under which health-care products are marketed in countries with differential powers to negotiate prices and questions of who foots the bill (the public, private individuals, charities?) and how (through taxes, crowdfunding, insurance?); and, second, to determine which approaches to health are ethical, fair and reliable enough to invest in, given the frequent over-claiming of the potential benefits of biomedical products under the pressure of competitive desire and a widespread confidence in a high-tech quick fix approach to health conditions. I discuss this through the work of biologist and theologian Celia Deane-Drummond, who reformulated some of these social issues in light of the ‘common good’ using a perspective of virtue ethics.

The example of ‘the alleviation of suffering’, a claim frequently made in proposals for regenerative medicine, genomics and high-tech applications in general, shows how without further specification regarding the number of people that might benefit from them and how much, the costs involved in therapy, how it is paid for and the potential harm to patients, there is potential for political corruption. In other words, the ‘common good’ referred to in claims of alleviation can easily be translated into public support for lucrative projects without genuine deliberation about the likely benefits of the populations that will be affected by them. In an age of over-diagnosis and overtreatment (cf. Haslam Reference Haslam2022: ch. 6), with movements to counteract this through organisations such as Too Much Medicine (BMJ 2023), Choose Wisely (Choose Wisely UK 2023) and Prudent Healthcare (IWA 2017), reflection on the ‘common good’ needs to be accompanied by a critical evaluation of the motivation and attitudes of those involved in research and marketing projects. Discussing the ethics of biotechnology, Deane-Drummond (Reference Deane-Drummond2004: 92) proposes to embed the notions of prudence and justice in social and political discourses to examine biotechnological projects. The notion of prudence, here, refers to the everyday practice of wisdom as a means of assessing relations, attitudes and motivations. ‘Prudence’ sets the way virtues need to be expressed in given circumstances, moving through deliberation, judgment and action in the community (Deane-Drummond Reference Deane-Drummond2004: 93–94).

Applying ‘prudence’ and ‘wisdom’ to deliberations on the common good of a new biotechnology in a community may turn out to be a ‘partial good’ when it benefits a few people at the expense of many, when health gains are minimal against the substantial healthcare of others or when achieved in undue haste. In global contexts, a critical eye needs to be caste on international collaborations that happen to coincide with regulatory differences or stark differences in wealth between the collaborating communities involved. Prudence tells us to interrogate the motivations of those responsible for or supporting such collaborations, including scientists, companies, state officials. It may also be important to query the practice of tempting scientists in LMICs into international research collaborations that overstate the benefits of research and health outcomes to their community. Wider needs and available resources of the community have to be taken into account, as an exaggerated passion about a particular new biotechnology towards a ‘health good’ can lack sensitivity about its long-term effects on both. Thus, communities with scarce healthcare resources may want to prevent that they are spent on high-tech quick fixes that entail long-term burdens and possibly irreversible health effects for the community (Haslam Reference Haslam2022). It is for this reason that the WHO and UN have argued for Universal Health Coverage (WHO 2017, 2022).

A key question relates to the need to focus resources on particular areas of biotechnology, when rather than the health of the local or national community, it mostly benefits the health or pockets of a few and leaves a majority without adequate primary care (UN 2016). Clarity should be given about the long-term costs associated with the development of regenerative medicine and the functions of its regulation (including, its ethics procedures and its relevance to national economic policies). The relative cost expended by LMICs, and also in HICs, may be in no proportion to any health benefits reaped (UN 2016; Polak Reference Polak, Cucchi and Darrow2022). Countries have hoped to save health budgets by relying primarily on public health systems that determine drug-intake on the basis of epidemiological statistics (Dumit Reference Dumit, Good, Fischer, Willen and DelVecchio Good2012), leaving communities with unaffordable high-tech and care poverty (WHO 2017; cf. Chapter 5). Other countries, such as Japan, have concluded that the only way forward is to shift resources within scientific research towards sustainable health, while stimulating self-help solutions rooted in local communities (Watanabe Reference Watanabe, Kodama and Hanabusa2018; NIHN 2022). Rather than the expensive option of having its elderly population commuting to hospital to participate in clinical trials, Japan has been investing far more of their health budget into preventative and integrated healthcare: from ’cure-seeking medical care’ to ‘cure- and support-seeking medical care’ (Iijima et al. Reference Iijima, Arai, Akishita, Endo, Ogasawara, Kashihara, Hayashi, Yumura, Yokode and Ouchi2021).

The effects of developing particular biotechnologies cannot be assessed by cost-benefit analysis alone and need to involve the judgement of the community and action. Judgement, here, involves memory (history and tradition, social context and culture), reason, understanding, ingenuity and its aptness; action involves building on deliberation and judgement and requires foresight, circumspection and caution (Deane-Drummond Reference Deane-Drummond2004: 93–94). Foresight tells us that a quick-fix of regenerative medicine will not resolve the world’s health conditions, as many of these are related to socio-cultural, economic and environmental practices; circumspection involves a clear perception of the reality of the applications of regenerative medicine, for example, its safety, such as the ability to control injected cells; and, caution deals with the risks involved in interaction with other health and environmental factors, such as stress, consumption and pollution (NHS 2020; Nesta 2023; WHO 2023). As many risks cannot be easily quantified, such as long-term risks and the synergies with other environments (for instance, cellular mutations can cause cancer), risk-benefit analysis alone in biotechnology is clearly inadequate.

In this virtue ethics approach, justice links virtue with wisdom and prudence: it frames appropriate ethical action owed to the community. Different from notions of rights, which force claims on others to provide equal opportunities usable only by some groups, justice involves morally binding action to accommodate differences between all people through duties and obligations towards, for instance, the excluded, the impoverished, the other-abled and non-human animals. Thus, when patent rights on regenerative therapy are violated by countries that have come to depend on them during clinical trials, but cannot afford them, the expectation of payment is morally unjust (Doval et al. Reference Doval, Shirali and Sinha2015): it would force the national community to use resources unjustly. Communities might decide to conduct more research into ‘primary prevention’ of medical conditions, such as those resulting from traffic accidents (spinal cord injury), working conditions (cardiovascular diseases, stress, cognitive decline), consumption (diabetes), modes of infection (HIV, STDs) and the living environments (cardiovascular diseases, cancer, stress) (EUSPR 2023). Alternatively, they might want to rely on societal research into what patients need/want before accepting company claims about patient needs. All in all, communities may want to re-evaluate the importance of primary care and social care. Higher appreciation of care work, care identity, the role of the environment and healthcare provided at the point of use (at home, work, in the local community), as provision rooted in the community might be preferable to overburdening hospitals with ‘social care’ (Haslam Reference Haslam2022: 202).

Deane-Drummond’s distinction between commutative justice, distributive justice and legal justice (2014) is also useful when considering current social and political practices of regenerative medicine. Commutative justice, which refers to what is owed between individuals following contracts, requires mutual respect and honouring commitments and the need for compensation when failing. Patient recruiters for experimental regenerative therapies that are unclear about the high risks involved do not conform to commutative justice; distributive justice concerns the socially just allocation of resources by those in power. This involves the fair and even-handed sharing of costs and benefits across time. But without the consultation of the population about high-risk national investment, regenerative medicine fails to conform to distributive justice; and legal justice pertains to regulatory relations between individuals and society as a whole. It restrains industry and healthcare providers to act responsibly towards individuals and the environment. But where brokered regulation is incentivised by competitive desire, regulation for regenerative medicine does not achieve legal justice.

Considerations of prudence and justice put into perspective the cost-benefit and risk-benefit analyses of the utilitarian approaches used by governments: they link the political deliberation on approaches to health to virtue ethics–based action in practice. When governments, similar to multinational pharma, are caught up in the vortex of competitive desire, their investment and regulatory policies will deprive their populations of a meaningful say in the deliberations on what kind of healthcare to develop, not just the programmes currently favoured on the basis of economic gains. Thus, long-term commitments of considerable funding of regenerative medicine for financial gain deprives people of choice. Apart from the ubiquity of overhyped scenarios of regenerative futures (Brown Reference Brown2003; Brown and Michael Reference Brown and Michael2003), populations currently have little to go on when considering how current healthcare investment might affect human and non-human life. And once large-scale investment in infrastructures is in place, choices will be path dependent (Page Reference Page2006), that is, pre-structured in directions that are not easily diverted.