ASIAN INNOVATION AWARDS: GOLD:
ASIA'S INVENTORS

Stem-Cell Secrets Unlocked

Singapore's leading embryonic stem-cell researcher
has made a major breakthrough that could see
stem cells delivering on their promise of cures
for terminal illnesses

By Trish Saywell/SINGAPORE
Issue cover-dated October 24, 2002

LONG BEFORE STEM CELLS became a buzzword
in the international scientific and medical community
and a focus of ethical debate, Ariff Bongso was
quietly unlocking the secrets of the mysterious cells
in human embryos. In 1994, Bongso became the first
to successfully isolate stem cells from a five-day-old
embryo and document that the cells could transform
themselves into any cell in the human body.

His research was published in the Oxford University
Press's prestigious journal Human Reproduction.

This year Bongso, a professor at the National
University of Singapore, announced another world first.
On August 5, he and his research team at the university
declared that they had successfully grown a human
embryonic, or hES, stem-cell line entirely without
mouse cells. The new hES cell line has been grown
on human feeder cells and cell nutrients.

The panel of five independent judges have declared
Bongso the Gold winner in the REVIEW'S
Asian Innovation Awards for this breakthrough.

It's a critical step forward in getting stem-cell research
to deliver on its promise of cures for diseases ranging
from diabetes to cancer. The ability to use stem-cell
lines grown entirely without exposure to mouse cells
eliminates one of the potential risks of pathogens
jumping from the animal feeder cells to the human
embryonic stem cells. Currently all of the 78 existing
stem-cell lines listed on the registry of the
National Institutes of Health in the United States
are supported or grown on animal--typically
mouse--feeder-cell layers. That rules them out for use
in clinical trials. "The discovery will definitely take us
one step closer to clinical applications," says Bongso.
"The whole idea is to take stem-cell research faster
to the bedside."

Bongso's methodology will be developed and used
as a research tool with the United States Food
and Drug Administration to create additional cell lines
for clinical applications. "The FDA is working with us
to develop a totally animal-free system and use it
as the gold standard," he says.

Bongso is now focusing his energy on unlocking
the genetic secrets of the cells and determining
which genes are responsible for instructing the cells
to develop into a particular tissue. Human embryonic
stem cells contain genetic instructions and can
be coaxed into becoming any of the 210 tissue
types found in the human body. They offer a way
of repairing or replacing damaged tissue and organs.

"From fertilization to pregnancy, genes are
continually being switched on telling stem cells
whether they should become a liver, or a heart,
or a pancreas or some other organ in the body,"
he explains. "If we can find out which genes are
responsible for making which organ in the body,
we will have hit a gold mine. Then all you have
to do is extract the genes, put them into a
stem cell, and it can become the tissue that
you want it to be."

At the same time, Bongso is also working on
developing safer storage systems for stem-cell lines.
Currently, the cells are stored by putting them
in open plastic straws and freezing them in liquid
nitrogen. But the method is not ideal because
the liquid nitrogen, if contaminated with an
organism or virus, could infect the cells
in the straw.

So Bongso is developing an electronic system
that promises to cut the contamination risk.
He forecasts his new method--which has already
succeeded in a first round of trials--will be
available for commercial use by the middle
of next year.

ETHICAL BOUNDARIES

In the last six months, more than 25 individuals
and groups from Asia, Europe and the U.S.
have contacted Bongso to work with him
on stem-cell research. "This is front-line research,"
he explains. "We have the cells, we have the
experience and we've got informed patient consent
[to use stem cells extracted from their embryos]."

Bongso is also one of the founders of the
Singapore-registered stem-cell research company
ES Cell International--which has six of the world's
78 stem-cell lines produced from human embryos.

ES Cell is one of only about 10 groups listed
by the U.S. National Institutes of Health that have
stem-cell lines eligible for federal funding.

The company has provided stem-cell lines
to more than 40 laboratories around the world.

Bongso tips his hat to the Singapore government
for embracing a more progressive stance on stem-cell
research than many other governments in the world.

Earlier this year, Singapore accepted
recommendations from a government-appointed
ethics committee on embryonic stem-cell research.

The new guidelines, which must still be passed
into law, allow scientists in the city state to withdraw
stem cells from adult human tissues,
aborted foetuses and surplus embryos
from fertility treatment as long as the embryos
are less than 14 days old. The guidelines
also allow scientists, under strict regulation
and on a case-by-case basis, to obtain stem cells
by cloning technology. The technique, referred to as
"therapeutic cloning," is permitted to create
human embryos for research purposes.

The guidelines completely ban human reproductive
cloning.

The new guidelines, closely modelled on Britain's
embryonic stem-cell research laws--are among
the most progressive in the world and will put
Singapore squarely on the stem-cell research map
worldwide. "I'm very pleased with Singapore's rules,"
Bongso says. "There are checks and balances.
The rules allow us to do our research
and at the same time keep a close eye on us."

Bongso started his career in 1976 as a veterinarian
specializing in animal-embryo transfer technology.
He obtained an undergraduate degree in veterinary
medicine in Sri Lanka and won a prestigious
Canadian Commonwealth Scholarship
to complete his masters and doctorate
at Guelph University in Canada.

Bongso later made the switch to in-vitro
fertilization work for childless couples
in the mid- 1980s. In addition to his teaching
and research responsibilities at the National
University of Singapore, he is the scientific
director of the in-vitro fertilization programme
at the National University Hospital.

Bongso, whose Dutch mother died of cancer
and whose Sri Lankan father died of a haemorrhagic
stroke, fervently believes that finding cures
for disease through stem-cell research
and the field of regenerative medicine
holds tremendous promise for those suffering
from terminal diseases. "As scientists
we must work within our ethical boundaries
and we can't play God," he explains.
"Some people might think it's immoral
to do research on embryonic stem cells.
But I can argue that it's immoral to deny
a sick patient a potential treatment."

The 56-year-old scientist is reluctant to say
how long it will take before stem cells
'can be used to generate specific tissues.
'But he predicts the fastest breakthroughs
will be in forming pancreatic cells-- perhaps
in as little as five to 10 years.

Last week, researchers in the U.S. announced
that insulin- producing stem cells could lead
'to a cure for Type 1 diabetes in which the body's
immune system attacks cells in the
insulin-making parts of the pancreas.

Despite his latest breakthrough, it remains
slow work: "We have a lot to learn about these
'cells," Bongso says. "They're very mysterious.
But the joy and happiness I get in doing research
that will eventually benefit mankind
is what spurs me on."

SOURCE: Far Eastern Economic Review
http://www.feer.com/articles/2002/0210_24/p038innov.html

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