Innovation amidst post-socialist reform: Jonas Salk and the birth of the Sabin strains-derived inactivated polio vaccine in China

Abstract

As an industrial science, vaccinology is susceptible to changing social, economic and political frameworks. This article reconstructs the history of the birth of the Sabin strains-derived inactivated polio vaccine (sIPV) in China. The development of this nascent vaccine can be attributed first and foremost to the circulation of knowledge and technology in the global polio research network of the 1980s, before the privatization of vaccine manufacturing and the escalation of intellectual-property protections. Tracing correspondence between Jonas Salk and a Chinese scientist, Jiang Shude, and his colleagues, we chart how institutional efforts in search of a profitable product and scientists’ motives in pursuing personal careers in the post-socialist reform era led to collaboration on many levels, centered around polio vaccines. In response to recent polio history research, we also emphasize the impact of multiple temporalities of polio dramaturgy on the vaccine manufacturer, as this article demonstrates how the confluence of shifting global polio eradication agendas and contingencies in complex vaccinology undertakings ironically helped to materialize the idea of the sIPV. Finally, stories of vaccines and scientists in China add compelling subplots to the global polio history, which reveals the need to reconsider the politicization of imported technology in broader socialist contexts.

A letter dated ‘3 June 1986’ was mailed from Jonas Salk to Jiang Shude (姜述德). Jiang had been an unknown vaccinologist working at the Institute of Medical Biology (IMB) in Flower Red Cave in the Western Hills of Kunming, in south-western China. Salk had visited two years earlier to discuss the feasibility of the IMB's proposal to manufacture inactivated polio vaccine (IPV). The initial collaborative plan had come to a halt by the time Salk wrote the letter to Jiang; still, he kindly offered Jiang an opportunity to travel to Bilthoven and then Lyon to learn IPV-related technology with a generous $10,000 grant for his one-year stay in Europe.¹

Transit time for mail between San Diego and Kunming was ten days or longer in those days. Even as such, page after page of letters, sometimes with misunderstandings due to language barriers, paved the way for the development of the Sabin strains-derived inactivated polio vaccine (sIPV), for which the IMB secured licensure in China in 2015. Using archives from Jiang's family archival collection and Jonas Salk's papers at the University of California, San Diego, this article elucidates the intricate transnational nexuses into which Jiang tapped to develop the vaccine, involving global polio eradication agendas, international loan assistance, and Jonas Salk's IPV rehabilitation plan.² On top of these, the impact of the timing of policies along the way to developing the vaccine cannot be understated. We argue that the multiple temporalities in polio dramaturgy, on personal, institutional, and global levels, not only map onto those left behind post-epidemic – the patients and specialized hospitals discussed by Dóra Vargha – but also onto the vaccine manufacturers.³

Vaccine development is resource-intensive. It entails conflict over values of ‘public-health priorities’ and ‘commercial opportunity’, and collaborative work with a myriad of interested parties. To this extent, Blume and Geesink categorize vaccinology as an industrial science susceptible to the social, political and economic frameworks that it inhabits.⁴ In non-Western contexts previously thought of as the periphery of vaccine development, recent revisionist histography has showcased the intellectual, institutional and sociopolitical opportunities that rendered countries in question conducive to participating in such scientific ventures.⁵ Building upon work in this vein, we pay particular attention to the impact on public-sector vaccine manufacturers of a historical confluence of China's post-socialist economic reform policies (i.e. the Reform and Opening Up) in the 1980s and the global childhood immunization campaign – the Expanded Programme on Immunization (EPI). The economic reform reconfigured the mode of operation in vaccine institutes, spurring them to venture into new profitable products as they were shouldering the task of supplying low-margin EPI vaccines across China.

Similar though it might look to the wave of privatization of public-sector vaccine producers in Europe in the 1980s, such as the National Institute of Public Health and the Environment (RIVM) in the Netherlands, the reform confronting the IMB in China was an example of state-orchestrated marketization.⁶ One unique attribute in our case is the scientists’ stance and response to the new profit-oriented environment. Unlike RIVM, where scientists generally resisted the course of privatization, embracing a market economy in reform-era China bore with it a politically graced connotation, legitimating scientists’ inclination to pursue personal careers and improve employee welfare. These personal and institutional motives are the lynchpin in sketching the profile of collaborations with Jonas Salk. Meanwhile, like RIVM, the IMB encountered the same trend of the standardization of indigenous vaccines, whereas we add the question of technological incompetence in the broader fields surrounding vaccine manufacture, for example pharmaceutical packaging material as inconspicuous as eye-drop tubes, that impeded China's standardization catch-up process from fulfilling the World Health Organization (WHO) criteria for liquid-drop oral polio vaccine (OPV). As a result, contingency in highly sophisticated vaccinology undertakings created room for future innovation; that is, the sIPV.

This article also adds to the historiography on polio vaccines, an area in which scholarly interest continues to grow.⁷ Shortly after the rollout of Jonas Salk's IPV in 1955, another American scientist, Albert Sabin, developed an alternative polio vaccine – OPV, which contains live, attenuated virus strains. The next decade saw a global switch to OPV as it was cost-effective, was favourable to both health staff and recipients (i.e. taken orally without needles) and presumably had better efficacy. The mass adoption of OPV soon proved risky since it could induce paralytic polio (VAPP) (although this was rare) and vaccine-derived viruses (cVDPV) in recipients. These two risks have been established as major threats to the current global polio eradication effort, especially in countries like China where wild polioviruses have been eradicated.⁸ Early in the 1970s, in view of OPV's imperfections, Salk and his colleagues in Europe created the Forum for the Advancement of Immunization Research (FAIR) to restore the use of IPV. In large part, the FAIR's efforts failed, and it was not until the twenty-first century that IPV re-emerged, for which reasons have been examined in studies by Baylac-Paouly, Hendriks and Blume.⁹ From FAIR members, Jiang managed to learn critical knowledge and techniques for combining Sabin's OPV strains and Salk's inactivation approach. Thus, we suggest, the FAIR's work was probably not a complete failure, and may have even been a vital repository for reconstructing histories of vaccine knowledge transfer.

Salk's IPV was never used in China in the 1950s, and nationwide polio vaccination only commenced in 1964 after Gu Fangzhou (顾方舟), a Chinese virologist, had succeeded in producing OPV in a candy dragée formulation. That Gu became an exclusive proxy of Sabin's OPV makes China a nuanced case, compared to its socialist counterparts, such as Hungary.¹⁰ Just as the study of the history of contested heart–lung machines in India demonstrates how nationalist ideas can ‘assign moral and technological value to local manufacturing’, we interrogate the cascading politicization of polio vaccines to show how political tension around the candy dragée OPV exerted continual influence on contemporary understandings of medical technology in China.¹¹ In doing so, this article also reaffirms the call to reconsider the lasting impact of hidden subplots in polio narratives.

The ‘Candy Dragée Grandpa’ and the oral polio vaccine in China

Gu Fangzhou matriculated to Peking Medical College in Beijing and became a Communist Party member in 1948. A year later, the Chinese Communist Party founded the People's Republic of China. From 1951 to 1955, Gu received doctoral training as a virologist in the Soviet Union. Reportedly, Gu's interest in polio arose from a polio outbreak in Nantong, Jiangsu Province, in 1953. Upon his arrival in Beijing from the Soviet Union, he started working at the Chinese Academy of Medical Sciences (CAMS) as the head of the polio research division. During the so-called ‘honeymoon time’ of China–Soviet relations, which lasted until 1960, Gu and three other scientists in China were sent to the Soviet Union to study polio vaccines. The team had initially planned to study Salk's vaccine, but happened to learn of an OPV field trial in Moscow in 1959. Gu acquired the three thousand doses of OPV from his former teacher at the Institute for Poliomyelitis Research, Mikhail Petrovich Chumakov.¹² Gu explained his choice of OPV, as it was suitable for China's economic and public-health conditions. Moreover, it seems that Gu had concealed the controversy over the safety of Sabin's vaccine in the Soviet Union, as Hungarian scientists had done around the same period.¹³

Relying on Sabin's virus strains from Chumakov, Gu quickly replicated the preparation of OPV at the National Vaccine and Serum Institute in Beijing (the Beijing Institute). Still, he needed to find a facility with a large rhesus monkey population to scale up production.¹⁴ Yunnan Province was a suitable option, due to its large monkey populations inhabiting the tropical rainforest scattered throughout the southern part of the province bordering Myanmar and Laos. They selected a location for an OPV plant, later known as the IMB, in Kunming, Yunnan's capital city. By the end of March 1960, the Ministry of Health (MOH) had issued an OPV field trial plan to be implemented in ten cities, involving five million children aged from six months to five years.¹⁵

That same year, the Soviet Union started withdrawing researchers from China, marking the rift with the Soviet bloc and the end of medical technology aid to China. Two years earlier, Chinese leader Mao Zedong had launched the ‘Great Leap Forward’, an agricultural collectivization campaign which marked a clear-cut departure from the Soviet Union, and the rise of Mao's ‘self-reliance’ ideology in science and technology.¹⁶ Consequently, when copies of the OPV clinical-trial plan were sent to provincial health bureaus, the vaccine was referred to as having been ‘prepared by our country’, omitting any indication of OPV's Soviet origin, which could have led to its denunciation for political reasons. The political peril must have been etched into Gu's mind. Even when writing for the CAMS bulletin in the far more tolerant political environment of 1998, Gu emphasized that he was politically innocent because his polio research had started long before the rift between China and the Soviet Union.¹⁷

Gu seems to have been reluctant to hide the truth, and particularly reluctant to hide it from his colleagues overseas. In 1963, when he released the successful results of the OPV trial in China, he chose to publish in the English-language version of the Chinese Medical Journal. This was the Mao era, and thus, even in writing for a medical journal with a Western audience, Gu was vigilant enough only to say that the Sabin-strain OPV used in China's trial was from ‘Prof. M.P. Chumakov’.¹⁸ Gu's report might never have reached researchers abroad, and the journal ceased publication six years later during the heyday of the Cultural Revolution (1966–76), which resulted in a nationwide political purge of intellectuals, scientists and artists.

In 1964 Gu moved his family to Kunming, where he served as deputy director of the IMB for seven years. The IMB had been supplying OPV since the field trial in 1960; however, nationwide distribution needed to be more manageable. Yang Zhihe (杨志和), the former chief of the OPV sales department, remembered how hard it had been to distribute liquid-drop OPV in 1960 – they had used thermos bottles with ice cubes to maintain the vaccine at a low temperature when shipping. Factories in Kunming struggled to meet the massive demand for thermos bottles, and Yang had to ask whoever wanted to order the vaccine to send enough bottles to the IMB before shipping. However, the breakages of OPV vials continued to frustrate Yang until 1963, when the liquid-drop OPV was replaced by a new formulation – candy dragée.¹⁹

That year, Gu finally found the last puzzle piece for making candy dragée OPV. The candy dragée OPV had been used in the Soviet mass vaccination in 1959. Gu could have returned to Chumakov to learn more about it had Soviet–China relations not deteriorated the following year. Even though Gu had managed to copy a recipe for it, it took three years for him and Dong Dexiang (董德祥) – a member of Gu's team sent to the Soviet Union – to locate available tablet-coating machines in the Shanghai Xinyi Pharmaceutical Factory. It was only with these machines that they were able to mix viral liquid with milk powder and sucrose, and wrap it in a sugar coating. In the early 1970s, the IMB took over the production of candy dragée OPV from Shanghai and leased a large cold-storage warehouse from a local slaughterhouse near Kunming East Railway Station. By freezing the candy dragée OPV at –20℃ in the warehouse and then using double-layered wooden boxes with sawdust as insulation for shipping, the IMB expedited logistics in the 1970s, a time when cold-chain transport in China was challenging.²⁰

According to a compilation of research reports from a polio workshop held at the end of 1971 in Kunming, the OPV was distributed across China, and several provinces reported that they had even undertaken bold experiments on trivalent OPV by vaccinating children with all three virus types at one time.²¹ One of the peculiar imprints of scientific research during the Cultural Revolution was the anonymity of individual scientists, out of devotion to collectivism. Because of the downplay of personal performance and merit, not even Gu's own name appeared in writings of the time.

Resembling the making of the ‘Father of Hybrid Rice’ in post-socialist China, as related by Sigrid Schmalzer, Gu's name was unknown to most Chinese people until the government-led wave of rewriting scientists’ life stories in the mid-2010s.²² These official accounts reveal the backstory of polio in the United States and Gu's travel to the Soviet Union, but they exaggerate the backdrop of the Cold War technology blockade and isolationism, against which Gu is portrayed as single-handedly preparing the vaccine.²³ In one recent popular-science book often recommended to Chinese youth, the origin of the candy dragée formulation is misinterpreted as an idea that occurred to Gu when he saw his three-year-old son fancy a piece of candy over dinner.²⁴ These stories about Gu resonate with Chinese audiences precisely because of the stress on self-reliance in many official narratives in public life.²⁵ No less importantly, childhood reminiscence of sweetness from the vaccine is so emotionally intense that people in China are more than willing to address Gu as the ‘Candy Dragée Grandpa’, a name first used by the central media, thus lending further credibility to the official history.

In a history of polio vaccines in China, written in the post-Mao era, Gu clarified the Soviet origin of the OPV, but not of the candy dragée.²⁶ This was likely a way to emphasize the originality of his contribution. In 1978, the IMB was awarded the National Science Conference Prize for its work on OPV development, and Gu was elected vice president of the CAMS and of Peking Union Medical College, one of China's most prestigious medical schools. The year also saw the advent of profound economic reforms which were to reshape the IMB.

Reaching out to Jonas Salk

Under China's planned economy from 1949 to 1978, six institutes for biologicals under the MOH were established, in Beijing, Changchun, Shanghai, Wuhan, Chengdu and Lanzhou. They were arranged to produce viral and bacterial vaccines (e.g. BCG, DTP and measles) and distribute them to nearby provinces. The IMB was the seventh member and the only one dedicated solely to OPV production. As part of the public sector, their income from vaccine sales was to be remitted to the state. In return, the MOH would cover all materials and salary costs. Yet the situation was upended by the economic reform. In 1984, the Chinese government enacted the contractual-responsibility system in the scientific area, a decollectivization measure which had previously been implemented in agricultural production. This new policy legitimized scientific institutions’ pursuit of extra profits insofar as they were completing tasks which had been contracted by the state. The call for an aggressive march into the market economy met an ardent reception across institutions. Under the cloak of strengthening the linkage between science and the market, the central government froze the budget of the Chinese Academy of Sciences (CAS) to push it into economic activity. However, one (possibly unwelcome) result of this was that an enterprise owned by the CAS even opened a lucrative (and illegal) erotic bar for making a profit.²⁷

In vaccine manufacturing, the new policies created a state-orchestrated market economy that was not unencumbered. The MOH recommended exploring profit-oriented product portfolios as a ‘priority of development’ for all public-sector vaccine institutes.²⁸ Meanwhile, they had to continue supplying low-margin vaccines for national immunization programmes contracted by the state, as China had started implementing the WHO-led EPI in the early 1980s. Even though EPI vaccines were not lucrative, over the long run, loosened state control over institutes’ operations brought favourable financial autonomy. As Yang Zhihe recollected, the propitious ‘smell of the market’ promised employee bonuses from extra vaccine sales revenue.²⁹ Earning a profit and boosting their incomes was a tangible incentive for employees, including scientists. In previous decades, they had scraped by for life's necessities in the rationing system. At that time, IMB employees would even sneak candy dragée OPV for their children, as sweets were scarce: groups of their offspring would get together to let the sunshine melt the dangerous pills into harmless candy while they played.³⁰

The marketization also brought about uneven growth among the seven vaccine manufacturers. During the EPI, to achieve an OPV vaccination coverage rate of over 85 per cent among Chinese children, the MOH kept the OPV price low to alleviate the financial burden on the state.³¹ In the 1970s, the Beijing Institute had been responsible for supplying OPV in northern China, but it had since largely abandoned this low-margin product. In 1989, with the help of the MOH, Merck & Co. in the United States transferred genetic recombination hepatitis B vaccine technologies to the Beijing Institute.³² At that time, the hepatitis B vaccine was not yet covered by national immunization programmes. The state explained this as following the principle of ‘who benefits, who pays’.³³ At 12.5 yuan per dose, the hepatitis B vaccine was far more expensive than OPV, which was 0.2 yuan per dose.³⁴ The IMB was affiliated with the CAMS, and consequently it lacked equal access to the same overseas commercial opportunities from the MOH as the Beijing Institute.

Without new products, the IMB neither updated nor expanded vaccine production facilities from 1979 to 1988.³⁵ Thus it had to seek its own opportunities. Given the IMB's expertise in researching polioviruses, hope was pinned on Jonas Salk. In 1983, Dong Dexiang attended the International Symposium on Polio Control in Washington, DC, a meeting of celebrities in polio research, including Salk. The following year, IMB director Guo Ren (郭仁), drafted a collaboration plan with an invitation letter for Salk to visit China.³⁶ In the plan, Guo said,

If we may be able to obtain the technological knowledge and the necessary equipment for large scale production of inactivated poliovirus vaccine for use in China and for exportation to other countries if we could contribute in the way as well [sic].

Guo painted a rosy vision for Salk, in which the IMB had the potential to become an IPV supplier for both China and global markets. This must have provoked Salk's interest, as he was engaged with the FAIR's IPV rehabilitation plan.

Salk had no reason to reject the IMB's offer, even though there would be a long road fraught with bureaucratic bumps for American scientists to travel to China. An invitation from the IMB, a local institute, could not help Salk secure a visa. Salk still needed a mediator to navigate the formalities before travelling to China. To this end, he turned to a Chinese American sociologist, William T. Liu (刘融). Liu forwarded Salk's travel plan to the CAS, which had been overseeing international scientific affairs between China and capitalist countries. The Bureau of Foreign Affairs deputy chair at the CAS, Li Jiaxiang (李家祥), then agreed to pass the message on to the CAMS before telling Liu that Dr Salk ‘will be warmly welcomed’ by ‘the appropriate leadership’.³⁷

Only twelve hours before his departure time, Salk obtained a Chinese visa. In September 1984, he visited the IMB and spent thirteen days in China. Given his fascination with architecture, Salk also travelled to Xi'an, one of China's ancient dynastic capital cities.³⁸

The aborted IPV collaboration

A few months before Salk's visit, the MOH had applied for a World Bank loan project to improve rural health and preventive medicine in China. Part of this project was designed to help China's EPI vaccine meet WHO standards to facilitate local immunization programmes.³⁹ Unlike the switch to an acellular pertussis vaccine, which had been propelled by the call for geopolitical unification within the EU from Dutch parents, most Chinese parents of the 1980s had no way of knowing that the vaccines administered to their children were not compliant with WHO requirements.⁴⁰ The major concern of the MOH and vaccine institutes lay in profitability: they could not sell vaccines to the global market without WHO qualification.⁴¹

The IMB filed a proposal for this loan project as well. As reported in an office memorandum from the World Bank, the IMB's ideal plan was to produce both OPV and IPV with a total investment of US$5.4 million.⁴² However, the MOH was loath to allocate much of the loan to the OPV facility's improvement alone. Guo kept quiet about the loan project during Salk's visit, as he might have foreseen the possible resolution from the MOH. Two days before Salk left Kunming, Guo discussed the money issue as a necessity of collaboration. In Guo's scheming mind, unveiling the lack of political will for IPV from the authorities in China would likely impede further opportunities from Salk. Instead, he told Salk that the IPV production capacity would be limited without foreign investment. As if the Chinese government had agreed to adopt it, he then bragged that the IMB could produce as many as fifty to two hundred million doses of IPV with overseas funding, of which two-thirds would be sold to other countries.⁴³

Before long, Salk realized that Guo's plan seemed too good to be true. After the journey to Kunming, Salk met his colleagues in Geneva. He had heard that the Institut Mérieux had received a visit request from the Chinese MOH regarding OPV. He subsequently wrote to Guo and received Guo's affirmation of the loan project. Guo explained that he preferred the IPV approach over OPV, even if the loan would be used on OPV facilities. After showing his determination, Guo hoped that Salk could provide support in ‘another way’, which meant direct funding from Salk or his connections.⁴⁴

However, Salk misunderstood Guo's implied meaning of ‘another way’, probably due to cultural and language differences. Salk thought that Guo wanted him to lobby members of the Chinese delegation sent to Lyon. On 22 November 1984, Salk got the attendant list and background information for the Lyon meeting from the Institut Mérieux. The WHO believed that vaccines produced in China could not meet its standards due to the lack of air purification, sterilization and clean water supply. Therefore the World Bank's intention for the loan project was to purchase the same production facilities as the Institut Mérieux.⁴⁵ Although it seemed that Chinese officials would not be interested in IPV, Salk promised Guo, ‘I shall make every effort to further the plan that you have in mind and we have discussed’.⁴⁶ With the progress of the new enhanced IPV and eIPV–DTP combination vaccines recently procured by RIVM, and evidence from a series of clinical trials conducted by the FAIR in Africa, Salk could find a niche for IPV in the market of developing countries with challenging public-health infrastructure.⁴⁷ He then charted a commercially promising future for Guo:

Many more doses of poliovirus vaccine are being produced in China than necessary if a more effective and stabile vaccine was available – one that does not require the deep freeze cold chain and that would require fewer doses. Such a vaccine … could then also engage in export.⁴⁸

Regrettably, the Lyon meeting shattered their illusions, as the Chinese delegation dismissed the IPV proposal due to the higher initial investment it would entail. But what made Salk believe that IPV still had a chance in China was that he had learned that a funding shortage was the only obstacle; the immunological controversy over OPV and IPV which had transpired in the United States would not be a problem. As early as in Geneva, Salk had learned that China tended to assemble vaccine facilities internally piece by piece, rather than utilizing turnkey technology transfer. The World Bank preferred the latter course since they suspected that the quality of the vaccines could not be guaranteed by assembling the ‘scattered pieces’ in China.⁴⁹ Salk had agreed with the World Bank's suggestion, telling Guo, ‘It seems advisable to acquire a completed facility for producing vaccine rather than try to … assemble a plant yourselves.’⁵⁰ Salk had changed his mind in favour of the Chinese choice after the Lyon meeting because he had hoped the piece-by-piece approach would reduce the total costs and increase the possibility of adopting IPV in China.

Salk shared his opinion with Guo, suggesting that ‘the modernization of vaccine manufacturing in China’ could incorporate IPV. He even persuaded Guo that the IMB's desire for IPV could also be ‘what is the desire to China’.⁵¹ However, he was so perplexed by Guo's reaction that he continued asking for extra funding. Salk soon rephrased his idea to Guo, to make it more understandable:

An IPV production facility could be established in China, along with other technologies in which the Chinese Ministry of Health would be interested, as part of any technology transfer from the Merieux Institute that may be arranged and with their participation.⁵²

Guo never wrote back because what Salk had said mattered no more. Instead of reconsidering technology transfer approaches, the MOH decided to control the total budget by whittling down the number of candidate institutes to be included in the loan project. The resolution was that the loan would be focused on three vaccine manufacturers, rather than all seven of them, as initially had been intended, and all technology transfers would be turnkey contracts. The IMB eventually obtained a share of the loan to build a new OPV plant, and Guo abandoned the collaborative plan with Salk.

Guo never committed to the IPV plan; his ingratiation to Salk to facilitate the collaboration had been a means of acquiring funding for the institute. With the loan, the IMB soon relocated to a plot of land in central Kunming. Moving down from the Western Hills was more than geographical displacement; it also meant better urban housing conditions for scientists and staff. This so-called welfare housing in China distributed by one's ‘work unit’ (employer) also promised broader material benefits and services, such as children's education, that came with the property.⁵³ As Jiang Shude's son recalled, this relocation improved the lives of his family members since at least ‘my sister and I didn't need to catch the bus in the early morning to attend school down from the mountain’.⁵⁴ Now that the IMB's financial predicament had been ameliorated, Guo no longer needed to rely on the risky idea of using IPV to source funding, which could jeopardize the merit of the OPV pioneers, including Gu Fangzhou, the IMB's direct superior from the CAMS.

Complex interests embroiled in China's polio research might have already influenced the course of history during those years. In mid-1985, Dong planned for an IPV field trial in subtropical Guangxi, China, after the Institut Mérieux had provided him with two thousand doses of IPV. As a strategy of the FAIR, the subtropical trials had been designed to demonstrate IPV's superiority over OPV, which had proven to be underperforming, probably due to interference from other intestinal viruses prevalent in the tropics.⁵⁵ However, Dong never returned to Salk a report about the results of the IPV in China. At this point, our story reaches the realm of conjecture, but it is likely that Dong rejected the release of results for the IPV trial because of discontent. In his last letter to Salk, he complained that the Institut Mérieux had only given him IPV, but not IPV–DTP, even though he had mentioned his requirement back at the Lyon meeting. At the same time, according to an investigation record, an outbreak of polio coincided with the trial and raged across the area.⁵⁶ It is also plausible that the mass vaccination with OPV in Guangxi to control the endemic polio outbreak had contaminated the results of the IPV trial. Either way, the never-received results marked the end of collaboration with the IMB on the institutional level.

‘Using the same building, the same equipment’

While Salk was occupied with Guo and Dong, Jiang Shude never ceased writing to Salk to share his published articles and updates on the World Bank loan project. Jiang was assigned to work at the IMB in 1960 after he had graduated from Beijing Medical College. Initially, he worked for the production department, with a job harvesting viral stock from monkey kidney cells. Then a series of changes in the system of scientific institutions following the new economic policy redirected Jiang's career trajectory. In 1980, the promotion system for the institute's academic faculty, suspended during the Cultural Revolution, was restored; the IMB began recruiting its first cohort of graduate students.⁵⁷ In China, due to a long traditional culture of master–apprentice relationships among intellectuals, scientists exalted the qualification of supervisorship, hoping that students would press ahead with their supervisors’ research. Climbing this career ladder requires publications and research projects. In the early 1980s, one efficient way to publish was translating English research work by collecting daily paper digests. Jiang had to start learning English from scratch using a dictionary and Linguaphone English teaching records played on a phonograph, as Russian was the first foreign language taught to college students in the late 1950s.⁵⁸ Now, in his forties, as head of the OPV production department at the IMB, Jiang could take advantage of his English-language skills to apply for overseas visiting-researcher positions.

In 1983, Commonwealth Serum Laboratories (CSL) in Australia admitted Jiang as a visiting scientist. At CSL, Jiang first learned more about IPV progress from his colleagues, including Alan Hampson. Hampson had initially worked for a poliomyelitis vaccine R & D programme following the adoption of the Salk vaccine in Australia by Dr Percival Bazeley, a former team member in Salk's lab.⁵⁹ During his eleven-month stay, Jiang found it feasible to combine Salk's inactivation method with Sabin's attenuated virus strains when testing β-propiolactone as an inactivator on the Sabin strains.⁶⁰ Jiang hoped to explore this new idea further, but state-sponsored overseas research opportunities became competitive. Due to a growing trade deficit, partly caused by an influx of imports during the economic reform, the Chinese government ramped up the review procedure in 1986 before issuing permits to study overseas. It even stipulated that personal wages be used to offset overspending abroad.⁶¹ Jiang turned to Salk for help:

As you know … It is not easy for Chinese scientists to go abroad … Many Chinese scientists got support from overseas … I wish to have a chance on vaccinology like this … I'm sure that you'd like to help me [sic].

To be more convincing, he even mentioned Dong Dexiang's wife, Dr Cao, who had received $7,900 of funding to study in the United States for six months, including the return airfare.⁶²

This was not the first time Salk had received such requests from IMB scientists after his visit. One year earlier, Yang Xiaofeng (杨晓峰), Guo Ren's graduate student, had written to him, asking for a studentship and Salk's supervision to study polioviruses at the Salk Institute. Yang enclosed a list of publications with his résumé, but Salk had no means to read any of these pieces which had been published in Chinese. Jiang wrote his first letter to Salk in November 1984 with a draft article written in English on antibody-combining capacity. As an extension of the method used by Ulrich Krech, a pivotal member of Salk's laboratory in Pittsburgh, this piece was impressive enough for Salk to describe it in the reference letter as ‘a further development of work done in my laboratory more than 30 years ago and it could be a useful addition to the assays of vaccines’.⁶³ With this connection, Jiang eventually got what Salk called the ‘good fortune brought by the new year’. Salk generously said he would like very much to help Jiang obtain funding, and find him a place for his further research. With all compliments, he introduced Jiang to Toon van Wezel, the head of the laboratory of inactivated viral vaccines at RIVM, and other European colleagues: ‘Dr. Jiang Shude … is a fine person and a good scientist … [He] eagerly desires to develop KPV (killed polio vaccine) production in China.’⁶⁴ Salk contacted FAIR member Philippe Stoeckel in Paris to provide Jiang with US$10,000 for his one-year training at RIVM and the Institut Mérieux.⁶⁵ After a long summer of waiting, Jiang found that his journey would be postponed because of the sudden death of Toon van Wezel. For the whole of 1987, Jiang buried himself in rescheduling his research plan and preparing other paperwork for inspection from the Chinese government before obtaining permission to travel to Europe.

Jiang arrived at RIVM in April 1988 and spent nine months there before heading to the Institut Mérieux to learn vaccine quality control techniques. He accomplished two main projects in his research plan designed by Salk, including one on the inactivation of various strains of Type I poliovirus (one of three serological types) while monitoring D-antigen. Tracing D-antigen content retrieved after inactivation was essential to Jiang's later work on the sIPV.⁶⁶ A few months later, Jiang brought up the idea of the sIPV as his third project, for reasons that had much to do with practical considerations. He wrote to Salk shortly before he returned to China:

Now we start a new program that is production of IPV by using Sabin strain. I think that it is better to produce both OPV and IPV using same building, same equipment in China. Otherwise, it is difficult for us to produce IPV [sic].⁶⁷

This was the first time Salk had felt a spirit of collegiality in the protracted collaboration with China. Undeterred by these barriers, Jiang kept his commitment, figuring out a suitable way for China to use IPV. ‘The idea of [it] is very intelligent, indeed’, Salk complimented, and ‘this would allow you to begin to produce IPV sooner than might otherwise be possible’. Closing the letter, Salk said, ‘I do hope that we may be able to see each other before you return to China’.⁶⁸

Salk said ‘our paths may cross again very soon in Europe’ several times in his letters, but it never happened during Jiang's stay. Jiang returned to Kunming on 7 April 1989. A few weeks later, China was immersed in political upheaval when student-led protesters occupied Tiananmen Square; the ensuing ‘Tiananmen event’ was broadcast to the United States. Jiang continually shared his thoughts about further research on the sIPV, but he never heard from Salk again.⁶⁹ To protect Jiang from political implications, Salk had chosen not to answer the letters, as the Chinese government had accused the US, in particular, of manipulating the Tiananmen protest.⁷⁰ On the final page of Jiang's letters in Salk's archive collection, a sticky note narrates how Salk's political sensitivity had made this collegiality with Jiang a genuinely caring friendship. ‘By the time JS was ready to reply – Tiananmen Square exploded. Decision was to wait to hear from Jiang Shude. Sure he would know why. There has been no communication [sic].’ Academic exchange with the West paused for a short period after the event. Had the protest occurred one year earlier, Jiang might never have been able to travel to Europe.

Beyond personal efforts: a prophecy

The IMB–World Bank loan project was approved in June 1986.⁷¹ As planned, a new center for OPV production would be established with an annual capacity of 100 million doses. The project underwent several rounds of global bidding for equipment procurement until 1990, when it commenced. The reasons for the slow progress between 1986 and 1990 are primarily financial: the bids from several international pharmaceutical companies were much higher than expected. Considering the delay, the World Bank eventually had to agree on a semi-turnkey approach (or joint development) to collaborate with RIVM to continue the project.⁷² Due to his connections with the institution, Jiang was promoted to chief technology officer of the loan project.

In 1967, Toon van Wezel developed the microcarrier cell-culturing technique at RIVM, using tiny beads suspended in a fluid culture medium to provide anchorage surfaces for cells to grow. This cell-culturing technology can amplify the scale of cell and virus production, and hopefully, with continuous cell lines like Vero cells as a substitute for expensive monkey kidney cells, lower the cost of viral vaccines. Thus it was supposed to meet the demands of low-income countries.⁷³ In a brief historical account, Jen Hendriks used the transfer of microcarrier technology to China in the 1990s to exemplify RIVM's critical role in global health.⁷⁴ To be more exact, what should not be overlooked is the work of Chinese scientists. Several groups of staff from vaccine institutes, including the IMB, were sent to the Netherlands during this joint-development technology transfer. The assumed higher yields of some particular viruses were not achieved, and the Lanzhou and Shanghai institutes bore the loss of failed attempts to employ this technology on measles vaccines.⁷⁵

As Van Wezel had accomplished the experiment for the compatibility of microcarrier technology with wild polioviruses, the transplantation of this technique to cultivate Sabin's strains for OPV production proceeded smoothly.⁷⁶ The IMB finished the primary acceptance inspection for new OPV techniques at RIVM in 1996, but the transfer to China was again delayed due to insufficient funds. A financial crisis caused by exchange rate volatility and subsequent cost overruns arrived unexpectedly – from 1987, when the loan was originated, to 1992, the RMB declined in value nearly by 55 per cent.⁷⁷ In 1990, the IMB acquired US$15 million in extra funding from Rotary International, a powerful sponsor of polio elimination, but the budget gap remained large. Thus, in 1994, the World Bank suspended the procurement of production facilities. The financial crisis was finally resolved with further fundraising, including US$44 million from the Chinese government and US$5 million from the Dutch bilateral assistance programme. Despite the resolution, the loan project had to be extended by fifteen months, and mass production could only be expected by the early 2000s.

The new OPV that the IMB was supposed to supply after adopting Vero cells and microcarrier technology did not reduce costs, as had been expected; the plastic eye-drop tube was a sticking point. To align with the WHO standards, the IMB changed the new OPV's formulation from traditional candy dragée to the plastic eye-drop tubes used worldwide. OPV dosage for each recipient was fixed in the solid candy dragée: one pill per child. However, the liquid was measured in drops and thus depended on the accuracy of each drop. In 1996, technicians concluded that the accuracy of made-in-China eye-drop tubes could not reach the same level as those manufactured in Western countries.⁷⁸ Importing eye-drop tubes from Italy would further increase the costs after mass production began in the year 2000. As a result, the MOH was unwilling to pay this extra money, and thus suggested that the IMB keep the production of polio candy dragée for China while exporting liquid OPV to overseas markets. Nevertheless, the World Bank worried about the liabilities of the IMB.⁷⁹

In the year 2000, global polio immunization would experience a radical change that would derail the MOH's OPV exports, leaving the IMB at financial risk. That September, Jiang was invited to the WHO headquarters in Geneva to attend the Meeting on Polio Vaccines. There he learned that the focus of global polio control had shifted from eradicating poliomyelitis caused by wild strains to eliminating those caused by OPV strains. The time to realize Jiang and Salk's dream of producing IPV at the IMB was approaching. Regarding Jiang's imminent retirement the following year, his former students took over the sIPV project, while Jiang served as a consultant. To ensure that the capitally intensive new OPV facilities continued to be useful facing a gloomy OPV market in the near future, the sIPV development started with modifying the OPV facility for IPV production.⁸⁰ With hindsight, it happened in the way Jiang's prophecy had suggested, ‘using the same building, the same equipment’.

Conclusion

In 2015, Jiang's team brought the sIPV to market. The first inoculation was at a small community health centre in central Kunming on 1 July of that year. This is a politically laden date as the Chinese Communist Party was founded on this date in 1921. The tradition of presenting a new technology product as a gift to the Party dates back to Mao-era China. With the slogan ‘Chinese People's Own IPV’ printed on a red banner, it transcended the field of medicine and became a ceremonial moment. Politicization surrounded this nascent polio vaccine, preaching an empty narrative of self-reliance that masked the transnational backstory and Jiang's name. In 2019, the Chinese government posthumously awarded Gu the title ‘People's Scientist’. Jiang died the same year as Gu, but local media refused to cover his story. Among the many versions of Jiang's public speech drafts, he had crossed out his own story so as not to challenge Gu's merit or detract from OPV's accolades.

It would be unjust to blame the scientists at the IMB for denying polio vaccines as transnational endeavours. After all, they encountered seismic shifts in the political correctness of scientific work which could jeopardize their careers, or even their lives: the fall from grace of Soviet science after the Great Leap Forward, the playing down of personal contributions in the Cultural Revolution, a sudden turn to the scientific promotion system based on individual performance, and profit-oriented marketization. In the wake of these events, Gu, Dong, Guo and Jiang pursued their careers while having to warily perpetuate the politicized myth of the polio vaccine. It was a historically formed political quagmire that few Western counterparts had ever experienced.

The tale of polio vaccines in China goes beyond scientists’ personal interests and battles for honor. It prompts us to examine a kind of transnational solidarity, characterized by the low-friction circulation (relative to today) of public-health technology through institutional and personal connections that conferred benefits on epidemic control in a large swath of developing countries. In other words, to reconstruct a historical account of the birth of the sIPV in China is to rethink Jonas Salk's saying, ‘Could you patent the sun?’, against the current privatized regime of knowledge dominated by pharmaceutical conglomerates. To be sure, beyond China's efforts from the socialist period to the reform era, the control of poliomyelitis, first with the candy dragée OPV and then with the sIPV, was enmeshed in global scientific networks. The transnational dissemination of polio knowledge and technology unfolded at a time when vaccinology had yet to be regimented by intellectual-property protection, as concluded by Stuart Blume.⁸¹ Beginning with the indispensable helping hand of Jonas Salk, Jiang had tapped opportunities afforded by FAIR colleagues at RIVM and the Institut Mérieux. International organizations – the WHO, the World Bank and Rotary International – colluded with the Chinese government to exclusively focus on OPV to eradicate polio, neglecting the health risks posed by the attenuated live viruses. Even as such, vaccine manufacturing is a sophisticated technological undertaking in which experts like Jiang, with fine-grained expertise, could take advantage of production facilities’ malleability. The technique of cell culturing with microcarrier and Vero cells, which supposedly improved OPV manufacturing, was modified to develop the sIPV as a product running against the World Bank's initial intentions, but catering to post-eradication needs.

However, there was more to developing the sIPV than the free circulation of medical technology. Jiang's story also touches upon recent scholarship on temporality and contingency in history, which has been discussed in the case of oyster cultivation at the Hong Kong–China border as a temporal system.⁸² In this sense, the sIPV is, by all means, a product featuring temporality. The development process was fraught with historical contingencies: the timing of reform policies that propelled vaccine manufacturers to branch out into new profit growth areas, the unexpected delay and overrun of the loan project that put the IMB at risk of insolvency, and the faulty eye-drop tube that caused the IMB to lose the market for the new OPV. These events consumed time at their own rhythm, but were coincidentally consistent with justifying the need for the sIPV as a future product. As date stamps on the letters between Jiang and Salk silently marked the transit time for mailing, the slow communication also helped in this regard. Polioviruses have their own temporality too. Only when the wild polio strains were nearly eradicated in most countries after half a century of mass vaccination with OPV did the global polio agenda move to the next concern – the health risks caused by live viruses from OPV strains. It was not until then that the WHO recommended a switch to IPV in post-eradication countries.

The health of Chinese children is also a topic worthy of attention. In a detailed account of the failure of the FAIR's effort to restore IPV use in developing countries, Baylac-Paouly, Hendriks and Blume briefly mentioned that the negligence of IPV as an alternative approach had elicited moral condemnation among Indian scientists.⁸³ There is no evidence of similar resistance in China. However, when interrogating the moral stance of IMB researchers, we must consider public-health conditions and the broader socio-economic system. During the 1980s and 1990s, China implemented its national childhood vaccination programme with an underfunded public-health system, within which ‘barefoot doctors’, a legacy from the socialist period, had to purchase injection equipment themselves before vaccinating children in their villages.⁸⁴ IPV, which would require even more syringes, would be hard to extend to rural China. Besides, even though Salk and the FAIR recommended DTP–eIPV combination vaccines to lessen the burden on the public-health system, the rigid arrangement of vaccine production, which separated the IMB so that it only engaged with polio research, made it almost impossible to develop a combination vaccine in China.

Finally, no less important were the health inequalities structured by the so-called ‘two-tier innovation system’ on the neoliberal vaccination landscape.⁸⁵ The WHO confirmed China's polio-free status in the year 2000, but the phasing out of OPV has only progressed gradually. Up to this writing, the free four-dose sIPV vaccination schedule has only been available in some affluent provinces or municipalities with sufficient public finance, such as Shanghai. In other areas, including Kunming, the national free childhood vaccination programme only covers two doses of sIPV plus two doses of OPV. Parents can opt to pay for commercial products to upgrade the vaccination service for their children, including an expensive pentavalent vaccine (DTaP–Hib–IPV) from Sanofi-Pasteur, which acquired the Institut Mérieux's vaccine business. By paying for combination vaccines to minimize shots and hospital attendance, high-income families may diminish their chances of contracting nosocomial infections, especially during public-health emergencies like COVID-19. Ironically, there is probably no episode more ambivalent for historians to appraise the marketization of health care in China than the case of the sIPV – where the post-socialist reform was concurrently an opportunity for vaccine innovation and an unsettling commencement of income-associated health inequality in mass vaccination, a public-health practice previously undertaken with vaccines as public goods.⁸⁶