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November 8, 2005 Tuesday

Stem cell study here goes into hyperdrive

By Chang Ai-Lien , SCIENCE CORRESPONDENT

THEY make us who we are, and could also prove our undoing.

Stem cells are the omnipotent cells that start out as a tiny embryonic ball in a mother's womb before multiplying and transforming into every organ and body part that makes that perfect newborn. They even go on to shape growth into adulthood, later life and perhaps even how we die.

More and more, researchers believe cancer cells hold similar powers of endless regeneration, except that they run amok in the body.

On the flip side, the failure of stem cells to make replacement cells for those that die leads to degenerative diseases that afflict particularly the old, like the debilitating brain disease Alzheimer's.

It is in stem cells that researchers hope to find new treatments and even cures for such diseases.

The solution? To understand how such cells work and why they thrive, which will point the way to controlling them when they fail.

The close link between stem cells and disease has opened up a new frontier of science that has become one of the most competitive and impactful areas of research.

It brought about 500 doctors and scientists from all over the world here recently to discuss the best and most up-to-date research in stem cells, ageing and cancer.

Experts at the Keystone Symposia, one of the world's most prestigious scientific meetings, told The Straits Times about the promise of such research, and the challenges ahead.

Blood stem cell expert David Scadden of Massachusetts General Hospital, in the United States, said there were four main ways that stem cells could revolutionise medicine - by harnessing them to repair damaged tissue; by allowing scientists to study how disease progresses in a Petri dish, rather than, say, dissection of a patient who has already died from a disease; to develop new cancer treatments; and as vehicles to deliver drugs.

His research involves trying to understand the environment where stem cells reside, in efforts to stimulate them to increase production when repair is needed.

Genome Institute of Singapore (GIS) executive director Edison Liu, one of the organisers of the conference, said: 'This is going to be a very powerful way of looking at a very complex set of disorders.'

In greying Singapore , where one in four deaths is caused by cancer, research on the big C, as well on stem cells, is in hyperdrive.

Hundreds of researchers are involved, and the good work being done here was a reason why Singapore was chosen to host the five-day meeting - the first time it was held outside North America .

Research from local players such as the GIS and the Institute of Molecular and Cell Biology (IMCB) held its own against the best work being done internationally.

The GIS, for example, has developed technology that can swiftly pinpoint the genes affected when, say, a disease strikes, and has already used it to identify almost 100 previously unknown genes that have a role in cancer suppression.

It has attracted funding from the US National Institutes of Health, as well as collaborators such as Yale and Johns Hopkins universities.

At the IMCB, plans are under way to collaborate on cancer stem cells in leukaemia with a group led by Professor Irving Weissman of the Stanford University School of Medicine - a pioneer in stem cell research.

'They have some of the best people,' he said of the institute's team of researchers. 'I wanted to hire them but I lost.'

He said that out of the 100 to 1,000 billion cancerous cells in a typical patient, only 3 per cent were cancer stem cells capable of regenerating.

So the idea is to target these minority cells, something that conventional therapy usually fails to do.

Said Professor Liu: 'Our concept of cancer is fundamentally being turned on its head, and the implication for treatment is that we may have been killing the wrong cells.

'All the work we've been doing on primary tumours is really at the end stage, not the early, stem cell stage; we could have been barking up the wrong tree.'

Professor Edward Holmes , dean of the school of medicine at the University of California , San Diego , added: 'We may have been going about it all backwards.'

Treatments pioneered here mean that patients in Singapore could be among the first to enjoy the fruits, even during clinical trials.

Prof Weissman estimates animal trials for the leukaemia project should happen in one to three years, with human trials five years down the road if all goes smoothly.

While there is so much hope, the experts agree that there is still a long road ahead in the extremely complex field.

Key stumbling blocks include growing adult stem cells in the laboratory - which has had limited success so far - and understanding the right environments where they can thrive.

Even work on how to tell, say, a cancer stem cell apart from other cells is still in its infancy.

What is lacking is also the increased computational power to allow researchers not just to look at the workings of individual cells, but at tissues as a whole.

Dr Alan Colman, chief executive of Singapore-based stem cell research company ES Cell International, said: 'What is necessary is a lot more knowledge than we have now, and we can't be rushing forward.'

With venture capital drying up, it has been left to governments to take the lead in funding promising research.

California , for example, passed Proposition 71 a year ago - creating a US$3 billion (S$5 billion) fund for stem cell research. In Singapore , it was announced recently that stem cell research would receive a $70 million boost to encourage collaboration and provide infrastructure and training for scientists working in the field.

A lot of money indeed.

But in California , if such research can cut the US$300 billion health-care bill by just 1 per cent, the fund will pay for itself, said Prof Holmes.

For Singapore , the gamble will pay off not just in terms of jobs, investments and health-care savings, but in bringing better treatments to patients faster.

Agency for Science, Technology and Research chairman Philip Yeo, who attended most of the talks at the meeting, said the challenge is to translate research here into clinical applications.

This will involve building up scientific knowledge in researchers as well as doctors.

'Ultimately, this will benefit the patients,' he said.

ailien@sph.com.sg