Singapore Gains as Bush Suppresses Growth of Stem Cell Research

By Yoolim Lee

 Sept. 26 (Bloomberg) -- At Singapore's Bistro Fabulous, men and women from
the U.K., Germany, Russia and China, dressed in sandals and T-shirts, mingle
with locals as they sip drinks and nibble on chicken satay and spring rolls.
It could be a typical bar scene, until you listen in on the conversations:
The topics include mouse embryonic progenitors and cellular pluripotency.
This is a meeting of the Stem Cell Club, whose members include researchers
at the forefront of one of the most promising -- and controversial -- areas
of science today. They're in Singapore as part of its efforts to create a
globally competitive biomedical industry.
The city-state has lured star scientists such as Alan Colman, who helped
clone Dolly the sheep, and David Lane, who discovered a protein that
suppresses some tumors. ``What creates good science is a good scientific
community,'' says German researcher Gerald Udolph, 44, as he sips a Tiger
beer at Bistro Fabulous's alfresco bar, located in the $300 million
government- funded science park called Biopolis.
The city-state has spent more than $3 billion in a bid to transform its
economy into a knowledge-based one that relies less on manufacturing of
products like cell phones and modems and more on fields such as research.
`Not Interested' in Nobels
Science isn't an end in itself for Singapore, which built itself into Asia's
second-richest nation, as measured by gross domestic product per capita, in
little over a generation. ``I'm not interested in Nobel prizes -- they're
not tangible,'' says Philip Yeo, former chairman of the state's Agency for
Science, Technology and Research, known as A*STAR.
``Science is a means to upgrade the economy and create new jobs and new
industries for long-term economic growth.'' The government of Prime Minister
Lee Hsien Loong aims to create 15,000 jobs in the city-state of 4.5 million
people and boost annual production to 25 billion Singapore dollars (US$16.5
billion) by 2015.
Yeo can already point to tangible results. Annual output of drugs and
medical devices has quadrupled since 2000 to S$23 billion last year. In the
same period, the country created 10,571 new jobs, says Yeo, 61, who as head
of the Economic Development Board for 15 years led Singapore's efforts to
create its own electronics and chemicals industries.
Since 2001, more than 100 foreign drug makers and biomedical companies,
including GlaxoSmithKline Plc, Novartis AG and Pfizer Inc., have set up
factories here, attracted partly by patent enforcement that's the strictest
in Asia, according to Hong Kong-based Political & Economic Risk Consultancy
Ltd.
Bit Player in Biotech
Singapore is still a bit player in the global biotechnology industry. The
U.S. accounted for 76 percent of biotech's $73.5 billion in global revenue
last year, according to a May report by consulting firm Ernst & Young LLP.
Biotech companies raised almost $28 billion in investments and loans
worldwide last year -- the most since 2000, the year scientists first mapped
a draft sequence of the human genome, setting off excitement about the
potential to cure diseases through genetics.
Biotech revenue grew 14 percent last year, and the industry will probably
record its first annual profit by 2010, says Glen Giovannetti, global
biotechnology leader at New York- based Ernst & Young.
Singapore faces stiff competition in its bid to commercialize stem
cell-related research. Wealthy countries such as Australia, Japan and South
Korea are building stem cell industries of their own. And all of them are
competing with countries such as China, India and Thailand, some of which
have laxer safety standards and have already begun selling experimental stem
cell therapies.
A Decade for Drugs
It can take a decade or more for discoveries generated in labs to translate
into drugs or medical devices that can bring in revenue, says Curt Civin,
who is the Herman & Walter Samuelson professor of cancer research at Johns
Hopkins University School of Medicine in Baltimore.
``The successful centers of human embryonic stem cell research will need to
provide a decade of patient investment, where the payoff will be many
scientific articles and discoveries,'' Civin says. ``Only then can the
research pay off commercially.''
One area where Singapore is trying to distinguish itself is in stem cell
research. Embryonic stem cells, which are the human raw materials that can
grow into heart muscle, nerves or other organs, have the ability to divide
and renew themselves indefinitely.
Treatment for Diabetes, Alzheimer's
Understanding how the cells do this, scientists say, could hold the key to
treating some of mankind's most formidable conditions, including diabetes,
spinal cord injuries, heart failure, Parkinson's disease and Alzheimer's.
The cells could also be used to test new drugs.
In addition, scientists are doing research on adult stem cells, which reside
in various tissues, including brain, bone marrow, muscle and liver. Adult
stem cells can sometimes repair tissues that have become diseased or
damaged.
``In the long term, stem cells have a tremendous potential,'' says William
Chia, senior principal investigator at Temasek Life Sciences Laboratory, the
molecular biology and genetics research institute sponsored by Temasek
Holdings Pte, Singapore's state investment company.
Developing actual products that can pay back the investment could be years
or decades away, Chia says. ``There is this short-term view of 'Wow, this is
potentially possible in three years or five years,''' says Chia, who holds a
Ph.D. in biochemistry from Imperial College London. ``It's almost never
realistic.''
Destroying Embryos
The research is also contentious. Some stem cells are derived from embryos
that are donated or discarded by couples undergoing fertility treatments.
The embryos, which are a few days old, are destroyed in the process.
In the U.S., President George W. Bush has said such experiments pose ``moral
hazards.'' In August 2001, Bush cut off U.S. funding for research on all but
existing stem cell lines made from discarded human embryos. A stem cell line
is a group of cells derived from a single embryo; the U.S. has approved
research on 22 such cell lines that were created before August 2001.
Germany and Italy, among other countries, also restrict the use of human
embryonic stem cells in research.
Singapore gives its scientists a freer hand by permitting experiments that
use stem cells derived from embryos that are less than 14 days old. The
14-day cutoff represents the time at which an embryo develops irreversible
individuality, says Lim Pin, chairman of Singapore's Bioethics Advisory
Committee.
Human-Animal Hybrids
Ethics regulators around the world are facing daunting decisions, such as
whether to permit the creation of human- animal hybrids for research --
something the U.K.'s regulator, the Human Fertilisation and Embryology
Authority, approved in September. ``Our overall stance is that we are
prepared to go forward as much as possible,'' says Lim, 71, who has a Ph.D.
in medicine. He says Singapore does ban some types of research, such as
experiments to clone human beings.
Singapore attracts researchers from around the world with fewer restrictions
on stem cell research and the government's promise to limit the time they'll
need to spend on academic bureaucracy. Salary packages match those in the
U.S. and the U.K. Lane, 55, moved to the city-state from Scotland to head
the Institute of Molecular and Cell Biology in 2004.
``The U.S. is really messing up big-time,'' says Lane, a founder of Cyclacel
Pharmaceuticals Inc., a Berkeley Heights, New Jersey-based developer of
cancer treatment drugs.
`Fantastic Applicants'
In July, Lane also became chief executive officer of the Singapore
government's newly formed Experimental Therapeutics Center, which focuses on
discovering and developing new drugs. ``We're getting fantastic applicants
partly because things have gone badly wrong elsewhere,'' he says. In
September, Lane agreed to head a new research institute at the University of
Dundee, dividing his time between Singapore and Scotland.
Another of Singapore's hires was Victor Nurcombe, a cell biologist who says
he was once called ``immoral'' and ``a criminal'' during a radio debate in
his native Australia for supporting human embryonic stem cell research.
``These are pointless battles,'' says Nurcombe, who moved to Singapore after
being recruited by Yeo. ``Singapore simply realized that this is the way to
the future.''
The influx of foreign researchers is leading to greater scientific output.
Last year, Biopolis researchers published 335 papers in international
journals compared with 111 in 2001. Singapore has awarded a total of 15
patents so far in areas including virology and bioimaging tools, according
to the government's Economic Development Board.
Colman's Company
One of Singapore's most famous recruits is Colman, who became CEO of ES Cell
International Pte, a regenerative-medicine company that's largely funded by
Singapore investors, in 2002. The company owns and sells six of the 22 cell
lines approved by the U.S. National Institutes of Health for
experimentation. Last year, ES Cell generated new cell lines suitable for
clinical applications.
To make more discoveries, Singapore needs to produce more Ph.D.s of its own.
``The republic's educational system has not been geared toward creating the
kind of creative-minded individuals needed for real breakthroughs to
occur,'' says Kirpal Singh, professor of creativity at Singapore Management
University and author of Thinking Hats and Colored Turbans (Prentice Hall,
2003).
Local universities trained 520 science and technology Ph.D.s last year, or
115 per million of the population. That compared with 235 in Sweden, 177 in
Finland and 175 in Switzerland, according to A*STAR. Only 80 -- or 15
percent -- of those receiving Ph.D.s in Singapore were Singaporeans.
1,000 Ph.D.s
``Singapore has moved from engineering and manufacturing to science, so the
education for young people must change,'' Yeo says. ``It's a major change.''
The country's goal is to have 1,000 Ph.D.-level research scientists by 2015.
To reach that number, it's offering S$1 million scholarships to students for
study overseas. Some 700 such scholarships have been awarded since 2001. In
return, students must agree to work in Singapore for six years once they
graduate.
Singapore arguably was the true birthplace of human embryonic stem cell
research. The field's birth announcement came after James Thomson, a
biologist at the University of Wisconsin-Madison, isolated human stem cells
in a lab in 1998 and published his findings in the journal Science.
Yet stem cell researchers including Harvard University's Doug Melton and
Jeanne Loring from the Burnham Institute for Medical Research in La Jolla,
California, say a Singapore-based scientist was the first to isolate the
cells.
Isolating Cells
One September morning in 1993, in-vitro fertilization specialist Ariff
Bongso was gazing through a microscope at a five-day-old human embryo at his
lab in Singapore. ``An idea came like a flash,'' Bongso, now 61, recalls.
With training as both a reproductive biologist and a veterinarian, Bongso
remembered reading that a five-day-old mammalian embryo was made of two
parts: an inner clump of about 50 cells that was to form the fetus and an
outer necklace of cells that would form the placenta. Was it possible that
in human embryos the inner clump of cells were stem cells?
Using embryos donated by couples seeking fertility treatments, he was able
to show that stem cells also formed in human embryos on the fifth day. The
University of Wisconsin patented Thomson's work in 1998; Bongso did not
patent his.
A native of Sri Lanka who studied in Toronto, Bongso moved to Singapore in
1987 to develop research in the obstetrics department at the National
University of Singapore.
Products for Sale
Today, Bongso is studying ways of using embryonic stem cells as screening
tools for potential drugs for the pharmaceutical industry; creating
embryonic stem cells without using human embryos to avoid controversy; and
isolating stem cells from Wharton's jelly, a substance in the human
umbilical cord.
No therapeutic products derived from human embryonic stem cells have been
commercialized in Singapore so far. In the U.S., the only adult stem cell
product on the market now is Baltimore- based Osiris Therapeutics Inc.'s
Osteocel, which uses adult cells gathered from bone marrow to generate new
bone. The surgically implanted treatment costs as much as $10,000.
Bangkok-based TheraVitae Co. is selling its adult stem cell product,
VesCell, which is used to treat heart disease, in Thailand at about $35,000
per treatment.
In the U.S., Advanced Cell Technology Inc. and Geron Corp. are among the
companies working with embryonic stem cells to develop treatments for human
diseases. Menlo Park, California- based Geron hopes to win approval next
year from U.S. regulators to begin the first clinical studies using
embryonic cells in people.
Backlash Feared
Bongso says he worries that the rush to commercialize stem cell research
could have adverse effects. ``If it's not bona fide therapy, we will have a
backlash against the whole science,'' he says.
The global stem cell industry suffered a setback in 2004, after Hwang Woo
Suk, a stem cell researcher at Seoul National University, announced several
``breakthroughs'' that the university's investigative panel later found were
based on falsified data.
Looking back a decade, Bongso says things have changed. ``At that time, the
environment was 'publish or perish' as academics; we never made money out of
our research,'' Bongso says. ``Today, it's 'patent or perish.''' Bongso, who
works in a small windowless office at the hospital, says he personally
doesn't feel any pressure to produce patents.
Nearby, Biopolis's labs and glass-enclosed walkways are buzzing with some
2,000 scientists, technicians and administrators from more than 50
countries. The 2 million- square-foot (186,000-square-meter) complex houses
five public research institutes.
Patent Laws
Eli Lilly & Co., GlaxoSmithKline, Novartis and several other drug makers
have set up research and development labs here, lured partly by the
city-state's new intellectual property laws. The laws protect both
international patents and those granted in Singapore.
One change made to appeal to drug makers when the law was rewritten in 2004:
They can extend their 20-year patent terms by as much as five years if
they're waiting for regulatory approval to market a new product.
One of the recruits is Edison Liu, a prize-winning breast cancer researcher
from the U.S. National Cancer Institute in Bethesda, Maryland. A U.S.
citizen who was born in Hong Kong, Liu says he liked Singapore's vision of
transforming its economy. ``I was impressed with the intelligence of the
leadership and their willingness to try a new model,'' he says.
Most of all, he was attracted by the funding the government would give to
his projects. Although top scientists are paid well in Singapore, salary
wasn't a deciding factor, he says, declining to disclose numbers. ``I wanted
to make a difference in my field, and Singapore seemed like an ideal place
for research,'' he says.
Genome Research
Liu accepted a position as executive director of the Genome Institute of
Singapore, which focuses on cancer biology, infectious diseases, stem cell
research and the genetics of Pan- Asian populations.
Human genome research and the study of stem cells are related fields. Once
scientists figure out a way to activate the genetic instructions for
becoming a liver cell inside a stem cell, for example, it might be possible
to repair damaged liver tissue in patients, Liu, 55, says.
``Here, I feel that I'm doing something very innovative,'' says Liu, who
became a permanent resident of Singapore this year. ``I wouldn't be anywhere
else right now.''
Last year, a group of Liu's scientists led by Lim Sai Kiang discovered a way
to enhance the development of human embryonic stem cell-based therapies by
using the less-potent daughter stem cells -- those created when a stem cell
divides.
Australians Recruited
Nurcombe, the Australian cell biologist, moved to Singapore along with Simon
Cool, his longtime collaborator at the University of Queensland in Brisbane,
and their entire team of eight researchers and postdoctoral fellows in 2003.
Nurcombe says his team now produces from 10 to 20 papers a year compared
with the three to five they'd write when they were based in Australia,
largely because the scientists no longer have to spend time teaching or
tending to administrative tasks.
Nurcombe and Cool, who jokingly say their goal is to become ``fabulously
rich and fabulously famous'' by exploiting their research, say their adopted
environment brings challenges. ``There are no excuses,'' Cool says. ``If you
cannot do good work in Singapore, it's because you cannot do good work.''
Nurcombe and Cool are studying adult stem cells and trying to find ways of
stimulating them to multiply. They're also extracting compounds from stem
cells and using them to enhance tissue regeneration. A bone repair treatment
may be their first product to undergo a clinical trial, Nurcombe and Cool
say, without giving a time frame.
Lure of Funds
Fame didn't necessarily lead to riches for cloning expert Colman, who moved
to Singapore from the U.K. in 2001. He was attracted by the prospect of
raising funds for his stem cell research.
``I considered starting a small company in the U.S. or the U.K. with venture
capital, but it proved very difficult at that time to raise significant
funding,'' he says. Singapore seemed like an ideal fit, he says.
Obtaining private financing didn't turn out to be as easy as he hoped, even
with the change in venue. Colman, 58, stepped down from his post at ES Cell
in July and returned to the lab. He says investors were reluctant to keep
funding research at a company where the prospects of producing commercial
products -- and profits -- were uncertain. ``We just couldn't raise that
money,'' Colman says.
He declines to identify the investors in ES Cell, of which he's still a
board member. The company is focusing on trying to boost revenue by using
its stem cell lines to test drugs, rather than seeking new stem cell-related
treatments for diabetes and heart disease.
`An Academic Job'
Colman now works for the government as executive director of the Singapore
Stem Cell Consortium, which coordinates research and supports projects such
as the development of a stem cell bank. ``It's an academic job,'' he says.
He'll also be working as a principal investigator at the Institute of
Medical Biology, a stem cell lab that's based in Biopolis, where he'll study
various types of stem cells -- not just those from human embryos.
The difficulty of translating lab research into commercial applications is
what Lim, the head of Singapore's bioethics committee, says keeps him up at
night. Singapore needs its bet on biomedical science to succeed in order to
ensure future prosperity, says Lim, who remembers the poverty and bloody
racial riots on the street in the 1960s when the former British colony was
thrown out of a federation with Malaysia.
Lane says Singapore's prospects are good. ``You want to see outcomes that
you can measure, and measuring outcomes from research requires a reasonably
long time,'' he says. ``Will the government have the patience? Everything
indicates it will.'' For Singapore's investments in biotech to pay off, the
wait may be a long one.
To contact the reporter on this story: Yoolim Lee in Singapore at
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Last Updated: September 25, 2007 17:03 EDT











Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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