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From the new issue of the Chronicle of Higher Education. Tony Mazzaschi AAMC From the issue dated April 13, 2007 China Challenges the West in Stem-Cell Research Unconstrained by public debate, cities like Shanghai and Beijing lure scientists with new laboratories and grants By SUSAN BROWN In 1983, Sheng Huizhen did what many of China's brightest students do: She left to pursue research opportunities unavailable to her at home, first in Australia and then in the United States. Sixteen years later, in search of greater scientific freedom, she migrated again. This time she headed back to China. As a researcher who studies embryonic stem cells, Ms. Sheng found the climate in the United States limiting. Although she landed a postdoctoral fellowship at the National Institutes of Health, where she worked her way up to a permanent staff position, federal policy at the time barred her from using human embryos or the cells derived from them. China, however, embraced Ms. Sheng's work. The city of Shanghai in 1999 offered her $875,000 to set up a new center at her alma mater, Shanghai Jiao Tong University, to study embryonic stem cells. She now directs a group of more than 50 people who are working on several lines of research, seeking to make cells useful for treating disease. Restrictive policies and a frosty cultural climate in the United States and other countries have helped China recruit a group of stem-cell scientists who trained overseas and stayed there to establish careers. "One big difference between China and the U.S. is the public support" for the research, says Ms. Sheng. "In the United States, it's a constant battle to convince the public of its ethics." In the West's unease over experiments that destroy human embryos, China sees opportunity - a chance to assume a leading role in what many see as a promising line of research. "It is clear that China senses a comparative advantage and is racing to take it," says Myles Axton, editor of Nature Genetics, who co-chaired a session on stem cells at an international meeting in Hong Kong last month. He and others who have traveled to China say they are amazed by the gleaming new labs and generous start-up funds that China has provided. It seems a well-placed bet, says Mr. Axton, who has visited China three times in the past two years. "Each time I am astonished at the speed and success of the investments that have brought so many talented researchers home." But for the Chinese to emerge as a world leader in this, or any, scientific field, they will have to close a gap in communication. Until recently many Chinese scientists published only in Chinese-language journals. They may have made important advances only to have them go unrecognized. Lu Guangxiu, who runs a thriving fertility clinic at Xiangya Medical College, in Changsha, for example, may have been the first to clone human embryos, which could be used to derive stem cells matched to individual patients, but no one in the West noticed her paper, and she still works largely on her own. Even finding out what Chinese scientists are doing can be difficult, though the scientists returning from the West could form a crucial bridge across that gap. In 2004 the British government decided to assess progress in stem-cell research worldwide, in part to determine where best to make their own investments. They sent a delegation of scientists, lawyers, and experts in business to five Asian cities to find out what overseas scientists were doing. Stephen L. Minger, one of the delegates, whose group at King's College London was the first in Britain to establish a cell line from a human embryo, sees Chinese stem-cell science as an emerging force. "It's going like gangbusters there," he says, "The government has put almost unlimited resources in a few specific labs. The technology is sophisticated; they have some of the best-equipped labs I've ever seen. They're attracting back to China a lot of very good, well-trained scientists." This homeward migration after long academic journeys has become so common that the Chinese have a term for it. They call people who come back "sea turtles." The moniker plays on the words hai gui, an acronym for returnees from overseas that sounds like words for the wandering marine mammals, which return to their natal beaches to lay eggs. Some promising stem-cell researchers are among the sea turtles. Gao Shaorong has returned from an assistant professorship at the University of Connecticut to lead a lab at China's National Institute for Biological Sciences in Beijing. Zhao Chunhua worked at the University of Minnesota until the Chinese Academy of Sciences recruited him to lead a lab at the Institute of Hematology in Tianjin. And Zhou Qi studied at a university in France before returning to the Institute of Zoology in Beijing, where he is trying to clone a panda. Back to Beijing One of the scientists the British group visited was Deng Hongkui, who trained in the United States and is now a professor at Peking University. Mr. Deng co-directs a group of stem-cell researchers whose goal is to generate cells that could be used as treatments for disease. (See article at right.) By mimicking the changing chemical environment that embryonic and fetal cells encounter as they grow in the womb, Mr. Deng's group has managed to generate cells that secrete insulin or albumin, a liver protein. Many other groups have tried for insulin-producing cells, which could be used to treat diabetes. But Mr. Deng says he has had unusual success. Stem cells do not readily become insulin producing; it is easier to coax them into becoming nerve cells, for example. Even when researchers succeed, only a small fraction, 10 percent to 15 percent, convert. Mr. Deng claims to get nearly double that proportion. Before accepting his current position in Beijing, Mr. Deng spent a dozen years in the United States, first as a graduate student at the University of California at Los Angeles and then as a postdoctoral fellow at New York University. Later he directed research at ViaCell Inc., a biotech company in Cambridge, Mass. But a return trip to China in 2000 changed everything. Mr. Deng says he found China a much happier and more productive place than it had been when he first left home. Within a year, he had secured the professorship at Peking University. Although Westerners in the past have overlooked Chinese advances, Mr. Deng is avoiding that fate. He has delayed publishing his findings on human cells, which he says are now in press, in order to first secure intellectual-property rights to the process of developing potentially therapeutic cells. Mr. Deng is also going after one of the bottlenecks in stem-cell research: a scarcity of human eggs, which scientists say they need to make new embryos. Embryos are usually the product of an egg and sperm, but to clone an embryo to match an individual patient, scientists take the DNA from an ordinary cell and substitute it for the egg's DNA. Those cloned embryos could generate stem cells the patient's immune systems would accept, a goal many labs seek, but none have achieved. Mr. Deng's group is trying to manipulate stem cells so that they grow into eggs. If they succeed, they could generate a steady stream of eggs for research. Clarifying Ethics China's support for work with embryos does come with restrictions. China does not allow egg donation solely for research. And in keeping with ethical guidelines agreed on by researchers worldwide and adopted by China in 2003, patients undergoing fertility treatment must give informed consent for unused eggs or embryos to be used for experiments. Those safeguards, if enforced, would prevent the sorts of errors that derailed South Korea's cloning effort. Questions about undue pressure placed on women to donate eggs were part of what disgraced researcher Woo Suk Hwang. Not only did Dr. Hwang and some of his colleagues fake their results, he also allowed or encouraged women in his lab to donate eggs to the effort, in violation of ethical standards, which were established to protect women from being coerced to undergo the procedure. In response to the scandal, South Korea placed a two-year moratorium on cloning that uses human eggs. The National Bioethics Committee decided late last month to allow the work to continue in 2008, but only with eggs left over from fertility treatments. That concerns Park Se Pill, of Cheju National University, who was among the first researchers to establish a line of stem cells from human embryos. The nation needs to allow egg donation for research, he told The Korea Times: "Otherwise, I am afraid scientists might leave for countries that legalize research with fresh eggs." Scientists increasingly seek the most favorable political climates to do their work, wherever in the world they may find them. Singapore, for example, with a population of only 4.5 million, has recruited biotechnology talent from all over, some of it to work on stem cells. Many researchers come from nearby Australia, where until recently, work on human embryos was not allowed. Others are from Germany, where research that uses human embryos is criminal. China's Prospects Although China's investment in and tolerance for stem-cell research is the envy of at least some Western scientists, others question whether China will successfully compete with other countries, many of which are starting to pour money into the field. In a paper published in the New England Journal of Medicine last year, two business professors, Fiona Murray, of the Massachusetts Institute of Technology, and Debora Spar, of Harvard University, calculated that Chinese governments, both central and municipal, have spent only about $38-million on stem-cell research since 2000. The British government plans to spend nearly that much in each of the next two years, and California has pledged $3-billion over the next decade. Even the states of New Jersey, New York, and Connecticut plan to outspend all of China over that same time. Although money goes further in China, where salaries are lower, the differences in resources will be large. Ms. Murray and Ms. Spar also point out that collaboration among Chinese scientists is weak. "If scientific progress tends to progress through the interconnected findings of a broad group of investigators, then China does not seem to be building the domestic networks that one might expect to lead to breakthrough discoveries," they write. Collaboration, not just among themselves but with scientists from other countries, may help address a third concern - credibility. Xiangzhong Yang, who directs the regenerative-biology center at the University of Connecticut, is a Chinese scientist who came to the United States as a graduate student in 1983. Mr. Yang has chosen to stay, in part because the university created the center. Although he became a U.S. citizen in 1998, he frequently travels to China and has served as both a mentor to visiting scholars and to those who have returned. Mr. Yang thinks Chinese scientists need collaborators from other countries who have access to all the primary data to ensure that their work is accepted by top journals. Restrictions and Recognition Gaining wider recognition concerns many Chinese scientists. When the Guangzhou Institute of Biomedicine and Health held a conference on regenerative medicine last month that attracted stem-cell scientists from all over China, it included a session led by editors from the Nature Publishing Group and others on how to get research published. That advice may prove useful to scientists like Ms. Sheng, who despite her considerable experience had difficulty getting one of her most important findings published. Ms. Sheng's group in Shanghai was the first to extract and grow cells from a cloned human embryo. Although Ms. Sheng had published in top-tier journals like Science and Cell while working in the United States, and the finding was clearly a first, she had difficulty getting the results into three top journals. In fact, the paper was accepted by the Proceedings of the National Academy of Sciences - Ms. Sheng had even paid the page charges - but then it was pulled before it went to press. The reason for the withdrawal was never made clear to Ms. Sheng. Since nearly two years had gone by as she tried to get the results into print, she decided to publish her results in a Chinese journal to establish the primacy of their success. The journal she chose, Cell Research, is written in English, but edited mostly by Chinese scientists. (Nature Publishing Group now owns the journal.) Cell Research, particularly the online version, may make available the results of Chinese research (and not just stem-cell biology) to a wider audience. All of the abstracts and many of the key papers can be printed from the site without a subscription. Ms. Sheng's paper caught the attention of her Western colleagues and raised the ire of the Western public. Politicians and bloggers objected to her work because she slipped the genetic material from patients into rabbit eggs, rather than human eggs. This mix of human and animal in a clone has raised concern in Western countries. But Ms. Sheng points out that it may be more ethical to use animal eggs for the practice runs as they hone their cloning skills. "Human eggs are extremely precious," she says, noting that her group can use up to 60 a day. "It would be a waste" to use them for perfecting the technology, she says. Outside China, researchers are having a more difficult time gaining permission to do the same work. Australia narrowly approved legislation at the end of last year that will allow scientists to apply for a license to clone human embryos for research. Scientists in Britain are awaiting a decision, expected midsummer, on whether they will be allowed to pursue similar studies there. In the United States, therapeutic cloning is legal, but no federal money may be used for the research, including any studies of stem cells derived from cloned embryos. Ms. Sheng would not likely be leading her field if she had stayed in the United States. Like Mr. Deng, she returned to find China and her native city Shanghai transformed. "The city completely changed within the last 20 years," she says. "It used to be very primitive, in a way. Now you see the city has become very modernized, in every way." http://chronicle.com Section: Research & Publishing Volume 53, Issue 32, Page A15 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn