The proliferation of stem cell therapies in post-Mao China: problematizing ethical regulation

Abstract

Thousands of foreign patients have sought experimental stem cell therapies in China since 2001. Despite critical scrutiny from scientific experts and tightening guidelines on the conduct of translational medicine, stem cell clinics have continued to proliferate in contemporary China. This article delves beyond regulatory exteriors to provide an ethnographic account of why unauthorized stem cell clinics targeting foreign clients have flourished under “socialism with Chinese characteristics.” As the former emphasis on preventive care during Mao's era of collectivism has given way to a market-driven pursuit of high-tech interventions, changes in the political economy of healthcare have transformed China's urban medical system into a laboratory for entrepreneurial tactics. This article traces how medical entrepreneurs operate within and beyond the socialist market economy by co-opting public hospital facilities for private gain and capitalizing on the hope and hype over stem cell research to promote dubious procedures. Rather than producing biopolitical modes of governance, formal regulation in China often invites enterprising tactics and hybrid practices that ultimately remake the boundaries between public and private, as well as ethical and unethical.

Keywords:

• biopolitics
• ethics
• governance
• stem cell science
• China

Introduction

The notion of contemporary China as the “morally bankrupt ‘Wild East’ of biology” (Dennis 2002, p. 335) has become a trite phrase overused by Western journalists and vigorously countered by Chinese scholars and government officials. Citing scandals over poisoned toothpaste and tainted milk powder or rampant piracy of movies and software, foreign observers have bemoaned the lack of regulatory controls in the rapidly transforming People's Republic. Meanwhile, Chinese officials have emphasized tightening regulations and touted severe penalties for corrupt regulators such as the 2007 execution of Zheng Xiaoyu, the former director of China's State Food and Drug Administration.

In this article, I analyze the proliferation of Chinese stem cell clinics catering to foreign patients in order to problematize the notion of ethical regulation in post-Mao China. I focus on the lived experience of regulatory policies to question how state power, individual agency, and the pursuit of health intersect on the floors of hospital wards in urban China. Despite critical scrutiny from scientific experts and tightening guidelines regulating the conduct of stem cell research and experimental treatments, thousands of patients from over 100 countries have sought stem cell therapies in China since 2001. From Bangladesh and Belgium to the United States and the United Arab Emirates, people suffering from neurological disorders have entrusted their bodies to medical entrepreneurs in China offering “tomorrow's treatments today.”

The ambiguous political status of these border-crossing stem cell patients complicates the linkages between governance and life posited by theorists of biopolitics. While Foucault's (1978) foundational work highlighted the central role of the state in managing populations, more recent interpretations have emphasized the self-optimization of individual bodies predicated on notions of risk (Rabinow 1996, Rose 2007). Contributors to the September 2009 issue of New Genetics and Society have called for a revaluation of these European and American-based formulations of biopolitics in light of the rapid development of life sciences in Asia. Gottweis (2009, p. 202) and colleagues suggest the emergence of a distinctively Asian form of biopolitics that hinges upon strong state support for biotechnologies, “patterns of bad governance that ignore Western standards of human rights and ethics,” and the rise of “bionationalism.” Ong and Chen (2010) and their collaborators have continued the critical scrutiny of how nationalist mobilizations have intersected with emerging biotechnologies in various Asian milieus. Although these ethnographic case studies demonstrate the variety of biotech policies and projects in China (Chen 2009, Greenhalgh 2009, Chen 2010, Sung 2010), India (Glasner 2009, Sunder Rajan 2010), Japan (Sleeboom-Faulkner 2010), Singapore (Waldby 2009, Ong 2010, Thompson 2010), South Korea (Gottweis and Kim 2009, Thompson 2010), Taiwan (Liu 2010), and Vietnam (Wahlberg 2009), taken as a whole they revive attention to the effects of state power on optimizing the lives of citizen populations. But in the case of US patients seeking stem cell therapies in China, stringent regulations at home have encouraged them to look beyond their own national borders for alternatives, rather than submitting docilely to local grids of power. These “medical tourists” and “biotech pilgrims” (Song 2010) travel outside the jurisdictions of their home countries yet do not fall neatly within the regulatory regimes of receiving countries. Although many have been written off as incurable by the American medical establishment, they have found refuge as valued clients in the VIP wards of Chinese public hospitals. Their transnational experiences point us beyond biopolitical modes of governance targeting citizen-patients to hybrid practices emerging in the interstices of regulatory differences.

I have been tracking the development of stem cell and other experimental cell-based therapies on the ground in China since 2004. The analysis in this article draws on a larger research project that entailed 24 months of multi-sited ethnographic fieldwork at Chinese stem cell clinics, content analysis of websites and media reports, as well as interviews with patients, caregivers, biotech entrepreneurs, and medical personnel. In this article, I focus on the activities of Shenzhen Beike Biotechnology Company,1 which the prestigious scientific journal Nature dubbed “China's most prominent stem-cell therapy company” (Cyranoski 2009, 147). The company has received laudatory attention from media outlets around the world (e.g. Einhorn 2006, PressTV 2007, Cairns Post 2009, Mirror 2009). Beike has also been the focus of critical scrutiny by scientists and clinicians and was featured in New Genetics and Society as a case study illustrating an alternative mode of governance in translational stem cell research (Chen 2009). Based primarily on interviews with company representatives, Chen suggests that Beike's controversial inversion of the conventional “bench to bedside” model of translational medicine may no longer be viable with new regulations on the clinical application of medical technology (e.g. PRC Ministry of Health 2009). I probe beneath these regulatory exteriors to provide a deeper historical and ethnographic analysis of Beike's practices that complicates our understanding of legal and ethical regulation.

In this article, I set the stage for my analysis by first situating the Beike case study in the context of stem cell geopolitics. I then examine how medical entrepreneurs in China operate within and beyond the socialist market economy by co-opting public hospital facilities for private gain. In the final section, I demonstrate how these entrepreneurs capitalize on the hope and hype over stem cell research to leverage ethics itself as a marketing tool. Rather than halting dubious practices, legal and ethical regulations in China often channel entrepreneurial tactics in new and unexpected directions that may ironically produce contradictory results.

Lucrative ventures: the Shenzhen Beike Biotechnology Company

Stem cell clinics in China have capitalized on the patchwork of uneven policies regarding stem cell research in various countries to attract lucrative transnational clients, as clinics in India have done (Bharadwaj and Glasner 2009). Beike Biotechnology Company, for example, was established in 2005 by Sean Hu, a Chinese molecular biologist who had trained abroad in Sweden and Canada and returned home to set up a new biotech venture in the Shenzhen Hi-Tech Industrial Park. While the previous generation of Chinese scholars sought to remain in their adopted countries (particularly in the aftermath of the Tiananmen Square crackdown), Hu was part of a growing wave of returnees who sensed greater opportunities back home.

The city of Shenzhen offered particular advantages for biotech entrepreneurs such as Hu. Located just across the border from Hong Kong, Shenzhen was designated China's first “Special Economic Zone” (SEZ) in 1979 under the “opening and reform” policies of Chinese leader Deng Xiaoping. A key experiment in stimulating the country's development after a decade of stagnation during the Cultural Revolution, SEZs such as Shenzhen were designed to attract foreign investment particularly from “patriotic overseas Chinese and compatriots from Hong Kong” (Wu 1985, p. 133) with the goal of promoting industrial development and facilitating exports. Unlike major urban centers nearby such as Guangzhou, Shenzhen was exempt from provincial regulations. The Shenzhen government thus had significant leeway to implement policies encouraging economic development.

While headquartered in Shenzhen, Beike Biotech operated as a distributed network linking laboratories and hospitals in different areas of the country. CEO Sean Hu recruited scientists and clinicians working on stem cell culture and transplantation techniques such as Yang Bo, a neurosurgeon at the First Affiliated Hospital of Zhengzhou University in Henan Province, who began experimenting with stem cell therapies for patients with neurological disorders in 2001. Hu provided the catalyst for transforming these clinicians' research into a commercial enterprise.

From its inception, Beike pursued the lucrative potential in treating foreign clients. Hu partnered with foreign entrepreneurs operating in China such as Jonathan Hakim, an American expatriate who spoke Chinese fluently and had worked as an information technology and healthcare consultant in Hong Kong, Beijing, and Qingdao. Capitalizing on the potential of the Internet for direct-to-consumer marketing of new medical treatments, Hakim created a website called “China Stem Cell News” (http://www.stemcellschina.com/) which aggregated English-language reports on Chinese stem cell research and posted accounts of patients who had undergone stem cell treatment in China. The website initially featured a “Who is Who” section that profiled various stem cell researchers and treatment centers throughout the country, reflecting Hakim's interest in working with multiple purveyors of stem cell therapies. Although nominally a “news” source that purported to provide objective and comprehensive information, the China Stem Cell News website ultimately became a patient recruitment tool for a single company: Beike. Not surprisingly, the organization of the website reflected this transformation, replacing the researcher profiles with narrative-style “patient experiences” documenting the increasing numbers of people who underwent Beike's stem cell treatment. Hakim launched the partnership with a “news” flash on 27 September 2005 announcing “Beike to Treat Foreign Patients” (China Stem Cell News 2005a). Striking the pose of disinterested observers, the self-declared (but unidentified) “China Stem Cell Staff” noted that they had “witnessed some treatments, before during and after” which resulted in “impressive improvements.” To further reassure potential Western clients, the article declared that “one member of the Stem Cell China News group is a doctor from the US and has been to the facilities and feels they are up to standard along with the doctors” (China Stem Cell News 2005a). The unnamed doctor was Hakim's father, a US-based urologist. The article instructed interested patients to click on a link that generated an email to Hakim, who had agreed to coordinate the logistics of the transnational medical procedure on behalf of Beike.

The first foreign patient received Beike's stem cell treatment in November 2005. Bob was a retired sea captain from Texas suffering from amyotrophic lateral sclerosis. I had first met him seven months earlier in Beijing, where he had tried a different experimental surgery in the hopes of halting the disease that was steadily ravaging his muscles and compromising his ability to breathe. In exchange for serving as a reference for other interested clients and keeping a journal of his experiences which the company would publish on the China Stem Cell News website, Bob was offered a free course of the stem cell injections at the Nanshan District People's Hospital in Shenzhen. The “free” treatment still entailed significant expense for the retiree and his wife, as they had to pay for their own roundtrip airfare between Texas and Hong Kong, hospital fees, medical tests, housing expenses, and meals. Beike arranged a room for Bob in the VIP ward on the 20th floor of the hospital and provided five stem cell treatments derived from umbilical cord blood which would be injected over the course of a month into his spinal cord fluid via a lumbar puncture. These cells were flown in on the day of each procedure from Yang's laboratory in Zhenzhou and then injected by a Nanshan neurosurgeon. As Bob summarized his experience in his diary, “I am the very first foreign patient and the procedure in general is very experimental yet, so there was never a guarantee, but I admit to being a bit disappointed so far with my own results.” His diary was posted online together with an assessment from the China Stem Cell News staff: “Did not notice differences on his own but his friends say he is walking better. Slight increase in hand strength on both arms as tested by grip meter” (China Stem Cell News 2005b).

Since Bob's initial therapy at Nanshan Hospital in 2005, Beike claims that it has treated over 5,000 foreign patients. Positioning itself as “the most important Group in stem-cells treatment in China” (Beike 2007a), Beike's marketing brochure for European clients declares:

Beike's greatest strength and the key factor which differentiates us from other research initiatives is that we specialize in clinical applications. We know there are a lot of patients in countries around the world who could have a better quality of life and even extend their lives with the technology available … but don't have the chance because of politics, religion and bureaucracy. Our goal is to help those people. We take the most advanced biotechnological research in the world, specifically stem cell therapy, and apply it clinically at a rapid pace. (Beike 2007b)

Although critics have lambasted Beike for marketing unproven therapies to desperate patients, company representatives suggest that the real problem lies in extraneous red tape preventing people from getting the care they deserve. This framing deflects questions about the scientific challenges involved in translating laboratory results into useful clinical applications, shifting attention instead to the political debates stymieing patients' access to new treatments.

“Wearing a red hat”: the unintended effects of regulation

To understand why public Chinese hospitals such as Nanshan have collaborated with Beike to treat foreign patients with experimental stem cell therapies, we need to situate this development in the context of China's changing healthcare system. Once heralded internationally as an example of universal preventive care during Mao's era of collectivism, the Chinese healthcare system has faced tremendous pressure from conflicting state policies seeking to generate profits while preserving access to healthcare over the past 30 years (Blumenthal and Hsiao 2005). The central government significantly reduced public funding of state-owned health facilities beginning in the 1980s, following policies that proved successful in increasing the profitability and efficiency of agricultural and industrial sectors. But in seeking to ensure access to basic healthcare, the Ministry of Health also continued to enforce below-cost charges on a wide range of routine medical services. As a frustrated staff internist at an elite Beijing hospital complained to me, an appointment with him cost the same as using a public toilet.

These features of Chinese healthcare policy reflect the peculiar political economy of what Mao's successor Deng Xiaoping branded “socialism with Chinese characteristics”: a volatile combination of decentralization coupled with continued state control over strategic sectors. Although the central government maintained strict price controls on what it considered essential healthcare, it permitted hospitals to set their own fees for new medical services. Developing advanced medical technologies thus became one of the few legitimate means of generating revenues.

This trend has blossomed in the profit-driven priorities of “healthcare with Chinese characteristics,”2 emphasizing high-tech medical services at corresponding higher prices. Hospitals across the country have created elite wards offering a range of high-tech services catering to wealthy consumers – a particularly lucrative strategy for Nanshan Hospital, given its proximity to Hong Kong. Second-tier hospitals such as Nanshan have also turned to external sources to generate revenue. By reinventing themselves as real estate brokers, these hospitals “lease departments” [chuzu keshi ] or “contract out wards” [waibao keshi ] to medical entrepreneurs. While the PRC State Council (1994) has declared such conduct illegal, savvy medical entrepreneurs such as Beike's CEO Sean Hu circumvent these regulations by partnering with a network of medical universities and local governments. These hospitals thus gain institutional credibility and legal recognition as “academic partners” of a lucrative joint venture stimulating local economies.

Beike Biotech's partnership with second-tier public hospitals entails paying “cooperation” fees to house its clients in VIP rooms, utilize nursing services, and collaborate with local physicians. The company essentially conducts its own health-related activities within the public hospital – from recruiting patients and performing stem cell injections to setting fees and collecting payments – with little or no oversight from the contracting hospital. This model of operating “a hospital within a hospital” [yuan zhong yuan ] constitutes an alternative tactic often described in Chinese business circles as “wearing a red hat” [dai hong maozi ]. As sociologist David Wank discovered in his study of Chinese entrepreneurs in the southern coastal city Xiamen, another designated Special Economic Zone, private companies often sought legal registration as public enterprises as a cover for their business activities. These affiliations between entrepreneurs and local bureaucracies blurred the boundaries between private and public ownership. Partly stemming from the socialist valorization of public property and status, the phenomenon of “wearing a red hat” was also an eminently practical, profit-oriented tactic that enabled entrepreneurs to take advantage of tax breaks, acquire institutional legitimacy, and obtain other benefits. The public agency partnering with the private company also benefited from these business ties, as entrepreneurs paid to use the “often underutilized or idle assets of the public units such as real estate and machinery” (Wank 2001, p. 79).

Local crackdowns on hospital operations have little effect on the operations of a distributed network such as Beike. Because they are merely using space within a partner hospital, these biotech entrepreneurs can easily move to a new location should any problems arise. As a Beike client from Florida described in an online journal documenting his treatment in China: “The Dr's here in Shenzhen don't really want to do the surgical injection on me, and I want it done. Qingdao is where I am having surgery where they will cut in to the back of my neck and inject the stem cells directly in to the injury site.” (Allen 2006).

As Jerry's entry suggests, when faced with problems or challenges at one site, Beike representatives could easily make arrangements with a more cooperative site to satisfy the demands of their customers. In Jerry's case, doctors at Nanshan Hospital, who had been contracted by Beike to perform the stem cell injections in patients' private rooms either intravenously through the blood stream or into the spinal fluid via a lumbar puncture, balked at performing the more risky laminectomy which would involve exposing his spinal cord under general anesthesia in the operating room. Jerry thus travelled over 1,600 kilometers to a hospital in another province willing to perform the procedure. As his experience illustrates, while professional qualms of medical personnel or oversight by hospital administrators or even regional health bureaus may regulate unauthorized practices at one site, they have the unintended consequence of shifting questionable activities to another node in Beike's diffuse network.

Capitalizing on ethics: stem cell confusions and conflations

If legal regulations have little effect in governing Beike's overall operations, what about ethical guidelines? In this section, I demonstrate how ethics itself has become co-opted as a marketing tool in Beike's arsenal of business practices rather than serving as a normative guide to regulate dubious practices. Beike's patient-consumers cite the “ethical” nature of the company's cells as an important factor in their decision to become clients of the company. Beike achieves this feat by exploiting the controversy over embryonic versus adult stem cells.

All stem cells are undifferentiated cells which can give rise to various other types of cells, but embryonic stem cells theoretically have the most potential for clinical application since they are capable of becoming any other somatic (bodily) cell type. The scientific challenge that embryonic stem cell researchers have faced, however, is controlling the differentiation process in order to produce the specific desired cell type. “Adult” stem cells, such as hematopoietic and neural stem cells, specialize in the generation of a smaller range of cells usually limited to the tissue type in which the adult stem cell is located. Some researchers have claimed that these adult progenitor cells can produce the differentiated cells of another tissue type (Bjornson et al. 1999, Lagasse et al. 2000, Krause et al. 2001). Because research with adult stem cells does not require the destruction of human embryos, political and religious conservatives have seized upon this form of research as morally desirable even though intense debate remains in the scientific community over whether and to what extent these adult stem cells can in fact “transdifferentiate” (Anderson et al. 2001, Abkowitz 2002, Schwartz 2006).

Beike offers patients with neurological disorders injections of hematopoietic (blood-forming) stem cells delivered into the spinal fluid via a lumbar puncture or intravenously into the bloodstream. These adult stem cells are present in small quantities in umbilical cord blood as well as bone marrow, and they give rise to red and white blood cells, platelets, and other blood and immune cells. Beike's sales pitch to prospective clients emphasizes the moral differences between embryonic and adult stem cells while leaving out questions about the physiological mechanisms by which their proffered injections counter the neurological problems experienced by patients.

Jason travelled from Calgary to undergo stem cell therapy at one of Beike's affiliated hospitals in Hangzhou in March of 2009, 16 years after he was first diagnosed with multiple sclerosis. In his public blog hosted by the China Stem Cell News website, the Canadian explained the superior nature of the cells he would be receiving from the company:

The stem cells that I will be receiving are “ethically friendly” as I like to put it. Although China certainly didn't have the same ethical problems with doing research on embryonic stem cells as we had in North America, what their research found out was that the embryonic stem cells don't really work. They are, you might say, too adaptable. Apparently, as I understand it, when they tested them on animals, the animals grew really strange, awful, monstrous tumours with hairs and teeth and eyes and the like! They had no control over what kind of cell the embryonic stem cell would turn into. However, umbilical or plaacental [sic] stem cells (also called adult stem cells I believe) work very well, and are what I will be receiving, along with stem cells harvested from my own bone marrow. They are also, of course, ethically friendly. I find this fascinating as it makes the whole furor over stem cells rather moot! (Jason 2009)

In this Canadian patient's understanding, Beike's treatment offers the perfect alignment of ethics and efficacy: the unethical use of embryos is an uncontrollable, dangerous practice that resulted in “monstrous” consequences, while the “ethically friendly” umbilical cord and bone marrow stem cells conveniently “work very well.” Jason's explanation, as well as Beike's own promotional literature, offers notably little detail on how these cells might actually function once inside his body.

Marketing the “ethically friendly” nature of their treatment on the cellular level enables Beike executives to circumvent larger questions both about the scientific challenges involved in translational research and the moral quandaries of selling unproven therapies to patients. Beike's biotech entrepreneurs sidestep these discussions by advertising bone marrow and umbilical cord blood injections as a “safe” form of “stem cell therapy.” In fact, hematopoietic stem cells have been used clinically for nearly 40 years in the form of bone marrow transplantation to treat leukemia, but specifically as a way to repopulate blood cells following radiation or chemotherapy to destroy cancerous cells (Thomas et al. 1975). Beike's savvy marketing touting the safety of hematopoietic stem cells conveniently elides the lack of definitive evidence for whether these cells can produce the new neurons so ardently desired by those suffering from neurodegenerative conditions.

Furthermore, bone marrow and umbilical cord blood contain only a small percentage of hematopoietic stem cells. Although Beike claims that each “stem cell” injection it offers contains approximately 10 million cells (Beike 2007c), the specific details about its methods of cell purification are scant in its marketing materials and it has yet to publish any peer-reviewed scientific articles detailing its procedures. This is not a trivial question, as scientists have not yet developed consistent methods to purify the notoriously elusive hematopoietic stem cells found in bone marrow and umbilical cord blood.

The vast majority of so-called “stem cell therapies” being marketed to patients leverage the clinical history and ethical appeal of adult stem cells while capitalizing on the hope generated by embryonic stem cell research. Without the magical words “stem cell” attached to the experimental treatment, I doubt whether consumers would be so eager to sign up for Beike's services. But Beike's “stem cell” therapies may in fact be physiologically equivalent to injecting blood cells into patients' spinal columns – blood transfusions, in other words. Even if we accept Beike's (rather dubious) claims that it is providing over 10 million hematopoietic stem cells with each injection, these cells may just differentiate into red and white blood cells – if they even reach the site of injury or survive at all.

Conclusion: beyond regulatory exteriors

I have sought to move beyond regulatory exteriors in order to provide a deeper ethnographic analysis of why unauthorized stem cell clinics targeting foreign clients have flourished under “socialism with Chinese characteristics.” Social analysts have pointed to the “governance vacuum” and “lack of governance clarity” (Salter 2008, p. 153) as driving forces in the development of stem cell research in Asia. Glasner (2009, p. 288), for example, has argued that lax regulations and the lack of a statutory framework for enforcing guidelines have enabled “maverick scientists” in India to develop stem cell therapies in a “liminal space … without bureaucratically defined ethical approval.” The implication is that “more ethics” (i.e. establishing stricter guidelines) will enable better governance of these unruly practices.

But as Jacob and Riles (2007) have noted in their analysis of the “bureaucracies of virtue,” the institutionalization of ethical guidelines produces new (and often unintended) forms of agency and personhood. While Jacob, Riles, and their colleagues have focused on practices of informed consent, my ethnographic research on stem cell therapies suggests that formal regulation in China often invites enterprising tactics that constitute new relationships between clinician-entrepreneurs and patient-consumers. Beike's medical entrepreneurs operate within and beyond the socialist market economy by co-opting public hospital facilities for private gain and capitalizing on the hope and hype over stem cell research to leverage ethics itself as a marketing tool to attract lucrative foreign clients. These hybrid practices ultimately problematize the role of ethical regulation in governing transnational regimes of bioscience.

Acknowledgements

This research was supported by a US National Science Foundation Graduate Research Fellowship. I would like to thank the patients, caregivers, medical personnel, and entrepreneurs who shared their experiences with me. I am grateful to Margaret Sleeboom-Faulkner for inviting me to present the ideas discussed in this article at the 2008 symposium on “The social regulation of stem cell research” at the University of Sussex and the 2010 “International science and bioethics collaborations in Asia” colloquium at the University of Cambridge. I would also like to thank my colleagues at Washington University and the anonymous reviewers for New Genetics and Society for their helpful feedback.

Notes

Anthropologists have traditionally disguised the identities of people, institutions, and even places we analyze in our published work. But in an era when our informants post their own accounts online and our field sites are visited by journalists, anonymity has become increasingly untenable. Although I have continued to protect the identities of people who shared their experiences with me in confidence, I have chosen to cite the actual names of people and institutions in cases where I obtained information about them from publicly available sources such as blogs, websites, media reports, and corporate news releases. This commitment to openness is particularly important for companies marketing experimental treatments to vulnerable patients. Rather than leaving the task to journalists and press release writers, scholars should also analyze these practices publicly so that prospective families thinking of undergoing the procedures can make a more informed decision about their medical choices.

I invoke this phrase to underscore the contradictory nature of Chinese efforts to reform healthcare since the 1980s. In recent years, high level officials such as Gao Qiang, former Party Secretary of the Chinese Ministry of Health, have publicly acknowledged the failures of these earlier market-based reforms and emphasized providing for the public good as the essence of “the road to health development under socialism with Chinese characteristics” (Xinhua News Agency 2008).