China

The Chinese government has in recent years earmarked stem cell science for special investment. It calculates that if it can provide a supportive funding and academic environment, China could take a leading role in a high-profile and potentially very important field at a time when Chinese biotechnologists in general are struggling to compete on innovation with their Western counterparts.

The result is a growing patchwork of well-funded teams in China's major cities researching stem cells from adult, fetal and embryonic sources, some connected to large hospitals. Many of these teams are carrying out work of international standing and publishing in Western journals. A recent mission to China from the UK was impressed with what it saw, judging facilities in the labs it visited to be "superb" and government support "excellent". (1)

Overall, Chinese stem cell researchers are more focused on moving the science into the clinic than on understanding the basic mechanisms of stem cell biology. Scientists and clinicians are eager to pursue clinical trials of cell-based therapies and several such trials are now under way to treat brain injury, corneal disease and neurodegenerative illness. This focus reflects the Chinese government's wider approach to science, which is to concentrate funding on applied sciences rather than "blue skies" research.

The country faces fewer moral or public objections to the use of embryonic stem cells than many Western nations. The production of new human embryonic stem cell lines is legal, as is therapeutic cloning. Public opinion seems - as far as one can tell - to be largely positive and focused on the potential medical benefits rather than issues to do with moral status of embryos.

China's pursuit of success in this field has in recent years fuelled many perceptions in the West. These include on the one hand fears that China is intent on becoming a "cloning superpower" courtesy of lax regulations and research that would be considered unethical in a country like the UK; and on the other, a view that Chinese research is unreliable and unoriginal by international standards. This report attempts to get beyond these perceptions.

China's appetite for clinical success and its willingness to "think big" could be major pluses in partnerships with UK labs and teams, which tend to be more oriented toward academic success. Chinese science and technology officials think highly of the UK's scientific and regulatory leadership in stem cell science. The UK's reputation in this field puts it in a good position to work with Chinese officials and scientists to remove the major obstacle to international collaboration - namely, an under-developed system of ethical and regulatory oversight.

The visible evidence of China's investment in stem cell science is plain to see: shiny new labs and research centres full of high-tech equipment in the major cities; stem cell startup companies and university/hospital spin-outs financed out of the public purse; overseas Chinese scientists being lured back to China by the promise of competitive salaries and perks. Our estimates indicate that China funds stem cell research in the range of $4 - $10 million per year, but this figure is projected to increase dramatically. Part of the difficulty in obtaining a meaningful overall figure is that the in-country purchasing power of the Chinese RMB exceeds its formal exchange value. Another complication is that Chinese stem cell science - as with other Chinese biomedical research - is funded through a range of different channels. China's Ministry of Science and Technology (MoST) funds the bulk of the research directly, through general science and tech funding streams known as the 863 and 973 programmes. But stem cell labs and projects are also supported by a variety of other public funding bodies - the Chinese Academy of Sciences (CAS), the National Natural Science Foundation of China (NNSFC), local government science and technology commissions, and universities themselves.

MoST's goal for China's current five year plan (2001 - 2005) is to invest RMB 150 million (£10 million) in stem cell research. Over the next five years, the ministry is expected to spend between RMB 500 million (£33 million) and RMB 2 billion (£132 million), depending on how productive the science turns out to be.

Of the additional public/government organisations funding stem cell science in China, the CAS and NNSFC are the most important. Neither organisation was able to disclose how much it spends in this field, but both organisations have overall budgets smaller than that of the MoST.

Most of China's top university stem cell labs and centres have spun-off companies to commercialise their research. A typical example is SinoCells, a spin-out from the Peking University's Stem cell Research Centre, which aims to develop cryopreservation methods for stem cells and use stem cells in drug screening. Unlike similar spin-outs in the US, however, almost none of its funding comes from banks or private investors. Instead, the company has attracted some US$10 million in funding from various state funding grants since 2000.

SinoCells is not unusual: virtually all Chinese stem cell spin-outs are funded from the public purse, and inevitably this provokes scepticism internationally about the viability of their business models and long-term prospects. It is worth bearing in mind, however, that there are examples of Chinese university spin-outs in other fields which have developed into profitable businesses despite being wholly owned by the state. Moreover, China has little option but to fund stem cell start-ups with public money: the country suffers from a lack of venture capital and private seed money for high-risk technology start-ups of any sort.

In the absence of such investment funds, partnerships and business models are emerging in China which would be unheard of in the UK. One example is the Union Stem Cell & Gene Engineering Company Ltd (StemGene). It was incorporated in February 2001 with two principal share holders: the Institute of Haematology in Tianjin and the Shanghai Met Corp, an organisation involved in the import and export of textiles. The company was floated on the Shanghai Stock Exchange, raising US$30 million. However, this financing is not funding stem cell research directly - it is funding a new hospital which will in turn generate revenue for research.

Overall, a complex web of funding streams, together with the blurred lines that exist in China between public and private investment, make it hard to estimate the overall level of funds being invested in Chinese stem cell startups and spin-outs - and hard too to know the extent to which such investments are being driven by commerce as opposed to prestige.

Assessments of what China has achieved to date range from breathless accounts of China as a "cloning superpower" to unyielding scepticism of the reliability of China's science in this field.(The truth lies between these polar views.

Many Chinese teams continue to publish a lot of their work in Chinese language journals, which makes it hard for western teams to assess the research. However, the number of Chinese stem cell papers surfacing in English language journals is now growing. These papers, combined with lab visits such as the recent DTI mission from the UK, indicate that while China is not yet leaving other nations behind in stem cell achievements, and may in some areas still be lagging, it has notched up some important successes and has huge ambitions. In particular, Chinese scientists have:

• Produced 10 or more Chinese human embryonic stem cell lines. The total number of embryonic stem cell lines established to date in China is unclear but we know of six lines in Shanghai and four in Beijing. The six Shanghai lines were derived from "surplus" IVF embryos by a team led by Huizhen Sheng at Xinhua Hospital in Shanghai Second Medical University. Sheng aims to use embryonic stem cell lines to develop cell-based therapies capable of treating Duchenne muscular dystrophy. Her team published a paper describing the six cell lines in a mainstream English language journal this year. At the Peking University Stem Cell Research Center in Beijing, another of China's leading stem cell scientists Li Lingsong told visiting UK scientists in 2004 that his team had succeeded in isolating four human embryonic stem cell lines from "surplus" IVF embryos. Li reported that his team used some 19 embryos to generate the four stem cell lines-a high success rate. Li's team aims to use embryonic stem cells to develop cell-based therapies for Parkinson's Disease and diabetes.
• Carried out the first clinical trial of adult stem cells to treat patients with traumatic brain injury. At Huashan Hospital, part of Shanghai's famous Fudan university, a scientist and neurosurgeon called Jianhong Zhu is doing potentially ground-breaking work with adult stem cells. Zhu's team extracts adult neural stem cells from patients who suffer open head wounds, cultures the cells and then transplants them back into the site of injury in order to improve recovery. In a clinical trial, eight such patients with "chopstick injury" (in which a barbed bamboo chopstick is pushed into the head during an argument over a meal) fared better than eight matched controls who had open brain surgery but no cell grafting. The clinical study remains unpublished.
• Succeeded in cloning several animal species (goats, pigs, cattle, mice), including the first successful cloning of a rat. The rat project was a collaboration between a team led by Qi Zhou at the Institute of Zoology in Beijing (a major centre for the study of transgenic animal technology in China) and a French team and biotech company in Jouy-en-Josas in France.
• Successfully isolated and cultured stem cell lines from human fetuses with a view to carrying out large-scale transplantation studies in primates. This work is led by Yu (Alex) Zhang at the Cell Therapy Centre in Xuan Wu Hospital in Beijing. The main focus is using fetal stem cells as brain grafts to treat neurodegenerative conditions. The team has access to a very extensive primate centre in Southern China with about 6000 animals available for stem cell research.
• Set up cord blood stem cell banks. Research is conducted on cord blood at a number of centres across China and cord blood banks have been established in almost all of the provinces. The most striking is an umbilical cord blood bank in Tianjin, a major city within driving distance of Beijing. On a grand scale and awash with state-of-the-art equipment, the Tianjin Stem Cells Research Institute has impressed a number of UK scientific visitors. The company behind it runs two services from the facility, one a public service for the national government, the other a private service for fee-paying parents. The facility is capable of storing millions of samples and there are plans to build a 600-bed hospital on site. The banks' primary function is to store tissue for transplantation but it also provides access to tissue for research purposes.
• Published one of the first papers reporting the production of cloned human embryos for therapeutic research. In 2002 Lu Guangxiu, a stem-cell researcher and IVF expert at the Xiangya Medical College in Changsa, in central China, told reporters that her team had succeeded in creating cloned human embryos and keeping them alive long enough to harvest stem cells. If true, the claim means that China achieved this milestone before teams in the US, South Korean and the UK. In 2003 Lu published a paper describing the work in a Chinese language journal where it was largely ignored by Western scientists. The status of Lu's breakthrough remains unclear.

The Chinese government issued a declaration in 1998 explicitly banning reproductive cloning. However, China permits-and indeed encourages and funds-research on human embryonic stem cells and therapeutic cloning. In the international arena China is aligned with the UK in arguing that countries should be permitted to follow their own paths on therapeutic cloning. In December 2003 the Ministry of Science and Technology in China issued national guidelines which echo key elements of the UK's regulatory framework. The guidelines are widely seen as a response to the furore that broke out in 2001/2002 when a respectable Shanghai team - led by Huizhen Sheng - announced that it was generating stem cells by transferring nuclei from human skin into rabbit eggs. The goal was to develop a way of generating embryonic stem cells that did not require scarce human eggs. Concerned scientists and bioethicists in China rapidly mobilised public and official opinion against the project.

The MoST guidelines cover stem cells derived from ordinary human embryos as well as those derived from human embryos cloned from somatic cells, human fetuses and embryos generated by the parthenogenesis. In common with the UK's framework, the guidelines: prohibit reproductive cloning but permit therapeutic cloning; permit stem-cell experimentation on human embryos up to 14 days old but forbid it on older embryos; rule that all gametes and tissues must be voluntarily donated in accordance with the principle of informed consent and that research institutions proposing to experiment with human embryonic stem cells must establish an ethical committee to review the research; prohibit the implantation of human embryos used in stem cell research; and prohibit the buying and selling of human eggs, sperm, embryos and fetal tissue.

But China's approach to policing stem cell research differs from the UK's in important respects. It is based on guidelines, not state legislation, which are vague on detail. Researchers in China are not obliged to obtain a licence to carry out embryonic stem cell work and know-how and experience in ethical review are lacking. There is no system for overseeing compliance with the guidelines or for inspecting stem cell research facilities. Funding committees within MoST are responsible for checking project proposals to ensure that they comply with the rules - but not all stem cell projects are funded through the ministry.

A recent DTI mission to China found that the central importance of consent was accepted in all the research establishments they visited. The mission was unable, however, to establish what the notion of donor consent meant in practice or gain access to any copies of the consent forms used in the IVF clinics. With regard to fetal tissue and cord blood banking, the delegation was assured that parental consent was required but was again not granted access to the consent forms. Only at Huashan Hospital in Shanghai, where patients with brain injury were being re-implanted with their own cultured cells, was the DTI delegation shown the relevant consent form.

The speed with which some stem cell procedures are perceived to be moving into clinical tests has generated unease in the West. One example involves Huang Hongyun, a surgeon at the Xishan workers' sanitarium in Beijing who cultivates cells from fetuses and injects them into the brains and spines of patients with terminal neurological diseases. His results have led hundreds of Westerners to his Beijing surgery. Critical Western experts claim Huang is exploiting desperate people to hone a technique that has not yet undergone rigorous testing.

(1) Report from the DTi Globalwatch mission on stem cells to the Far East, 2005.

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copyright: © | last updated 24 November 2005