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

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

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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."

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