WSJ -- China Stem-Cell Research Surges As Western Nations Ponder Ethics
March 6, 2002
China Stem-Cell Research Surges As Western Nations Ponder Ethics
By KARBY LEGGETT and ANTONIO REGALADO
Staff Reporters of THE WALL STREET JOURNAL
CHANGSHA, China -- Last fall, a U.S. company said it had
accomplished a remarkable feat: producing the first-ever cloned human
embryo. But here in this tree-lined central Chinese city, that didn't sound
like such an impressive milestone.
Scientists at the Xiangya Medical College here claim to have cloned
dozens of human embryos over the past two years for medical-research
purposes. Moreover, say U.S. and Chinese scientists familiar with the
field, there are at least three other teams in China doing embryo-cloning
experiments. That's in sharp contrast to the U.S., where a heated debate
over the ethics of cloning has stalled most similar work.
"We're not that far behind [the West]
anymore," Lu Guangxiu, the professor who
leads the Xiangya team, said recently as she
strode through her fertility clinic and into the
stem-cell laboratory next door.
Indeed, her cloning project and others like it
are moving China to the forefront of some of
biotechnology's most controversial
technologies. To many Western scientists,
China's leap into embryo cloning lends
credence to their arguments that the
technology is all but unstoppable, despite any
ethical objections it might raise. Some even
predict that fears of falling behind in a biotech
race with China could spur the U.S. to set aside some of its misgivings.
"We will either condemn them [the Chinese] as godless members of an
evil empire, or we will say 'Hey, wait a second, we can't be left out of
this race,'" predicts Paul Berg, a Nobel laureate in chemistry at Stanford
University.
The Xiangya team's assertion that it cloned a human embryo two years
before the U.S. company, Advanced Cell Technology Inc., has yet to be
verified by independent experts abroad. But Prof. Lu, a fertility
specialist, published a paper in China in 2000 describing her cloning
efforts, and several Chinese and U.S. scientists who know of her work
say her claims are credible.
Earlier this year, after officials of the Hunan provincial government had
inspected her laboratory, they posted a report on one of the province's
official Web sites designating Prof. Lu's research as one the province's
most important scientific projects. Dou Zhongying, a highly regarded
stem-cell researcher in Shaanxi province, says he has applied for a grant
with Prof. Lu for a joint research project, and he describes her as
China's leader in the field.
Even so, scientists around the world are likely to remain skeptical of her
team's claims unless a recognized scientific journal publishes her
research. Prof. Lu says she hopes that will happen soon.
New Treatments
The 62-year-old Prof. Lu says she hopes her work will lead to new
medical treatments, but she is also enthusiastic about its commercial
potential. She has applied for personal patents covering her research.
Meanwhile, her research has helped her get most of the funding she
needs for a planned multimillion-dollar expansion of her fertility clinic.
Prof. Lu and her team are engaged in "therapeutic cloning," or cloning
human embryos in order to obtain stem cells. Unlike most adult cells,
whose functions are preprogrammed, embryonic stem cells can adapt
themselves to a variety of specialist roles, filling in as heart or nerve
cells. Researchers think they can exploit that versatility to develop new
ways of fighting such devastating diseases as Parkinson's or diabetes. Because they share the genetic
makeup of their donor, stem cells from cloned embryos theoretically could be transplanted into the donor's
body without being attacked as foreign invaders.
Though it is different than "reproductive cloning," or cloning that produces a live genetic twin of an
individual, therapeutic cloning is controversial because the days-old human embryos created in the lab to
produce the stem cells must be destroyed in order to harvest them. That outrages religious groups and
others in the West who believe that human life begins at conception. Still others fear it could put science on
a slippery slope toward reproductive cloning.
In the U.S., privately funded research on embryos is essentially unregulated. But most U.S. researchers rely
at least partly on government funding, and a 1995 law bars them from using federal funds to pursue any
research that harms or destroys a human embryo. So far, human-embryo cloning has been openly
attempted by only one U.S. company, Advanced Cell Technology, of Worcester, Mass.
Though he gave the go-ahead in August to limited U.S. funding for studies of stem cells left over from
fertility clinics, President Bush has condemned embryo cloning as "creating life for our convenience." In the
next several weeks, the U.S. Senate plans to consider legislation that would ban cloning for both
reproductive and research purposes. Tuesday, at a news conference and a Senate hearing, scientific and
patient-advocacy groups called on Congress to keep it legal to clone embryos for stem cells. Opponents of
the practice have launched a campaign deriding it as "clone and kill."
In China, where a different set of ethics prevails, Prof. Lu is relatively free to pursue her research. Few
Chinese would equate an embryo with a human being. That's one reason why China's policy makers are
rushing to embrace cloning as a potential tool for extending human life, cutting medical costs and delivering
better medical care.
Beijing has invested heavily in the biotech industry, setting up a national fund to finance researchers and lure
top Chinese scientists familiar with the latest technology back home from abroad. Some Chinese investors
also are forming relationships with leading research centers. At the Fudan University School of Medicine in
Shanghai, for example, Harvard-trained scientist Zhu Jianhong is studying brain stem cells with the help of a
fund set up by Hong Kong billionaire Li Ka-shing, as well as support from the government.
Rabbit Eggs
In a series of experiments that push the limits of science and ethics, Sheng Huizhen, a biologist at Shanghai
No. 2 Medical University, claims to have succeeded in deriving stem cells from embryos created by fusing
human tissue with the egg cells of rabbits. Rabbit eggs are more plentiful and easier to get than human eggs.
Dr. Sheng, a former employee of the U.S. National Institutes of Health in Maryland, presented her work
recently to scientists at the University of Texas's Southwestern Medical Center in Dallas. She declined to
comment for this article.
Some in Beijing hope the biotech revolution will provide China with what Sputnik gave the Soviet Union: an
entree into the ranks of scientifically advanced nations -- but with an even bigger commercial payout. For
now, its rapid gains in the field are likely at least to give it a prominent voice in shaping global biotech
policies.
Its moves into cloning and stem-cell technology also may complicate efforts in the U.S. and Europe to put
controls on those technologies. Last week, when the U.S. delegation to the United Nations argued for a ban
on all laboratory cloning, they met with firm opposition from China.
"We support enacting a ban on cloning a human being, but we think that we should encourage scientists to
do therapeutic cloning," says Li Lingsong, an adviser to China's large U.N. delegation. Dr. Li, a former
Stanford senior research fellow who now leads a stem-cell lab at Beijing University, says he thinks "it's
wrong to close the door" on promising research.
Drawing Attention
So far, Prof. Lu says she hasn't publicized her team's research except for a single notice in the Bulletin of
Hunan Medical University and the report on her work by the government, because she didn't want to "draw
attention." However, she and other Chinese scientists are beginning to realize that they need to subject their
work to scientific scrutiny in the West to win the global recognition they crave.
The Chinese "need an internationally reputable program," says Jerry Yang, a Chinese-born cloning
researcher at the University of Connecticut, "and they need to open their doors." Dr. Yang, a naturalized
U.S. citizen, says he has tried to use the influence his work in cattle cloning has given him in the field to
persuade Chinese scientists to make their progress known to the world.
Prof. Lu decided to begin work on cloning a human embryo in 1998. Earlier in her career, she had focused
on the reproductive problems of patients at her fertility clinic. She says that in June 1988 she successfully
created China's second test-tube baby. And she readily adopted other cutting-edge reproductive methods,
such as screening embryos for chromosomal abnormalities.
Because of China's strict one-child policy, government officials kept close tabs on her work -- warning her,
for example, against helping local women conceive twins, a service she says she sometimes provides for
foreign patients.
In cloning, her early progress was slow. Though her fertility clinic had government funding, Prof. Lu had
to struggle to purchase the equipment she needed to finance her cloning ambitions. In the late 1990s, with
government help, she expanded her clinic to two floors from one, a move that allowed her to take on more
patients. Her revenue jumped to about $2 million a year from just $50,000 in 1995. She pumped much of it
back into her research, along with other government money she received.
By 1999, dozens of women were coming to her clinic each day to take fertility drugs that helped them
ovulate. Since the cloning project would require large numbers of eggs as its starting material, Prof. Lu says
she asked her patients to donate their leftover eggs, as some fertility clinics do in the U.S. Some of her
patients agreed. The resulting bounty was passed to her researchers just a few doors down the hall.
A Major Advantage
"A lot of people don't have human eggs to conduct their research, but I do," she said as she passed a room
where several woman were resting on beds after undergoing artificial insemination. In the lobby, dozens
more were awaiting treatment.
In 1999, Prof. Lu says, her researchers successfully cloned their first human embryo by inserting DNA
from an adult cell into a human egg whose own genetic material had been removed. "I could hardly believe
our success at that moment," says Xie Changqing, a young scientist who took part in the work.
Later, Prof. Lu's team began to let the embryos grow to a more advanced stage so that their stem cells
could be harvested. She hired more researchers and poured even more money into the project, building a
row of spotless, airtight lab rooms just down the hall from her clinic.
With nearly a dozen full-time researchers dedicated to the project, Prof. Lu says they are making progress.
Nevertheless, cloning remains a largely trial-and-error process. In their first attempts, Prof. Lu says her
team tested techniques they had read about in overseas research journals. Copying the approach taken by
Scottish scientists who had cloned the sheep Dolly, she says they stripped a human egg of its DNA and
then injected it with the nucleus of an adult cell. But few of the embryos created in this way ever began
dividing, and many died before reaching the four-cell stage.
Preserving Ooplasm
Before long, they developed a new technique, with better results. Instead of first removing the egg's
nucleus, they left it intact and injected the donor cell alongside it. They then allowed both to grow, in some
cases for as long as 10 hours, before a team member would swoop in with a hollow needle to suck out the
egg nucleus just before it began to divide, leaving only the donor DNA. Under the old method, large
amounts of the egg's syrupy contents, known as ooplasm, were lost when the nucleus was removed. The
little-understood chemicals in the ooplasm allow the egg to return the donor-cell DNA to a more youthful
state in which it is capable of growing into an embryo.
The researchers say they also tried adding DNA from different types of cells to the egg, including skin cells
from aborted fetuses. They say that because these cells aren't yet fully developed, it might be easier for the
egg to reprogram their DNA.
Prof. Lu says that about 5% of embryos cloned in her lab now develop to the blastocyst stage, at which the
embryo is a hollow ball of about 200 cells. That's the stage at which stem cells first appear -- in a bump-like
structure known as the inner cell mass.
Prof. Lu and her researchers say they have been able to extract stem cells and maintain them in the
laboratory for three generations. However, they remain a long way away from establishing a robust
embryonic stem-cell line -- a continually replicating population of cells. Their ultimate goal is to keep the
cells dividing in their primitive state for years in the laboratory, generating an endless supply for experiments
in forming brain and other tissues that could someday help patients.
Prof. Lu says that, after a recent visit to a fertility clinic in Virginia, she realized how fast the science was
changing and that to stay ahead she needed to raise even more money. As a result, she has prodded the
government to increase her annual research grant, and she says she is talking with one of China's largest
companies, China International Trust & Investment Corp., about an investment in her fertility clinic. The
company, known as Citic, was also interested in taking a stake in her research operations, but Prof. Lu says
she refused. One of Citic's units confirmed that it has agreed to acquire a majority stake in her clinic for $3
million.
Prof. Lu's scientific reputation has gained her some political clout. The local government has appointed her
chairwoman of a provincial political body, and she travels frequently to Beijing, about 810 miles away, to
advise the government on biotechnology. With her newfound influence, she says she has started urging the
government to allow more private Chinese companies to become involved in the research.
Amid this heady rush of scientific activity, Beijing is beginning to express some qualms about the absence of
regulation. "We hope that our scientists will make breakthroughs in their research. But we don't want to see
any negative impact that could result from rushing forward blindly," says Wang Changrui, a spokesman for
the office that oversees scientific initiatives sponsored by the Ministry of Science and Technology. The
government is considering new laws, he says, but it isn't clear when they might be enacted.
In Changsha, Prof. Lu also wonders where her field is heading, and what it means for humanity. Though
she is opposed to it, she says she suspects advances in stem-cell research will eventually make it possible to
clone a human being. "It is," she says as she sits around the lunchtable with her researchers, "an irresistible
trend."
Write to Karby Leggett at karby.leggett@wsj.com and Antonio Regalado at antonio.regalado@wsj.com
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