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

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