Editor's Note: This is part one of a three-part series on global stem cell research. Parts two and three will run in Thursday and Friday's issues.

EDINBURGH, Scotland - Nine people crammed into a small elevator downtown here, as part of a media blitz to learn about stem cell research in the region.

The sign on the steel wall read "Maximum occupancy: 13 people," to which an Englishman commented, "Scottish people are smaller."

A Scotsman looked up and said, "Smaller, but heartier and more intelligent."

Chuckles abounded. The Scotsman, however, had a sturdy argument, considering scientists such as Ian Wilmut and Austin Smith reside in his country.

Wilmut, of the Roslin Institute, led the research team that cloned Dolly the sheep, and is just one of several scientists in Scotland now working on stem cell research. Smith heads the Institute for Stem Cell Research, which was formed through a partnership of the Medical Research Council and the University of Edinburgh. His research group is focused on characterizing the cellular and molecular mechanisms that govern the self-renewal and differentiation of embryonic stem cells (ESCs) of mouse, rat and human origin.

While stem cells have been used for more than 30 years in bone marrow transplantations, Smith said the scientists are looking for new generations of therapies that might benefit afflictions such as Huntington's disease and muscular dystrophy. But it may be several years away before the general public sees a therapy on the market.

"It's very difficult to give a reasonable prediction as to how long that will take," Smith told BioWorld Today. "The potential of these cells is just not all transplantation. It's the sexy thing that gets people excited, what it can do for diabetes, for Huntington's disease. But these cells have incredible potential as screening tools to develop new drugs."

With drug safety issues coming to light regarding Merck & Co. Inc.'s Vioxx and Biogen Idec Inc. and Elan Corp. plc's Tysabri, an early stage stem cell screening product for drug discovery would have tremendous value to the biotech industry. But finding therapeutic applications will take time, Smith said, adding that side effects from gene therapies provide a concrete example of why thorough research is so important.

"It's not possible to make a timeline," Smith said. "We have to learn from gene therapy and do this properly. Ultimately, the data we have are encouraging, but not definitive by any means."

Scotland is a country of 5 million people, perhaps best known for its bagpipes, castles and kilts. But it also became known for its science on July 5, 1996, when Dolly was born. She died almost seven years later with a bad case of osteoarthritis and now resides inside a glass case at the Royal Museum in Edinburgh.

"She demonstrated that differentiated adult cells could be reprogrammed back to the embryonic state," said Jim McWhir, a scientist who works with Wilmut at the Roslin Institute.

McWhir's team of scientists is working to develop a system to generate human embryonic stem cells from biopsy material in order to isolate ES-derived differentiated cells that could be used therapeutically.

Researchers are aware of the dangers that could arise if a patient injected with such a therapy receives an undifferentiated ESC, or an ESC that has not formed into the particular cell type targeted for injection.

"You would only need a very rare escapee to have that be a problem," Wilmut said.

McWhir added, "The idea is to engineer fail-safe features to protect against that risk of treatment."

The Roslin Institute scientists also are working on stem cell therapies in the area of orthopedic disease. They have determined that they can make bone in a culture vessel, as well as in an animal. They now are doing experiments to show they can repair bone in a preclinical model.

Wei Cui, who works side by side with Wilmut and McWhir, is focused on finding ways to use stem cells in improving the drug discovery process.

"One of the bottlenecks for drug discovery," she said, "is the toxicology."

By differentiating ESCs into liver stem cells, scientists will be able to test the toxicity of a drug long before it reaches humans.

While working with Cui and McWhir, Wilmut also is studying the potential of using cloning to discover therapies for amyotrophic lateral sclerosis, or Lou Gehrig's disease. Scientists know that of those with Lou Gehrig's disease 10 percent get it through an inherited gene. Of that 10 percent, 20 percent - or 2 percent overall - have the SOD1 causative gene. Despite 20 years of research, scientists still don't know why SOD1 causes the disease, and they have not been able to identify the other genes that cause it.

"The thing that cloning can let you do is to study the other 8 percent," Wilmut said.

He also noted that cancer could be studied by replicating the tissues found in patients that have the disease. And therapeutic cloning could be used to avoid problems of rejection, in which a patient's immune system refuses to accept the introduced stem cells. If the cells are genetically matched to the patient, there should be no immune reaction.

However, to do all of that research, Wilmut said he is a "wild optimist" and thinks that women eventually will consider donating their oocytes, providing more than the limited embryos available today. If people can see the benefits that come from the science, they may be more willing to support the research, he said.

Such progress also may translate into more funding for the scientists. A lot of the ESC work being done at the Roslin Institute is funded by Geron Corp., of Menlo Park, Calif.

The Institute for Stem Cell Research is part of the European Consortium for Stem Cell Research, or EuroStemCell, which is receiving €11.9 million (US$15.6 million) from the European Union during its four-year duration. That project, which Smith serves as chairman, involves 11 academic institutes and three enterprises across eight European countries.

Cui said sharing information between laboratories is crucial to success. She is traveling around Asia for an international exchange of technical data that will hopefully advance her work and that of the Roslin Institute.

"The results are just so scarce," she said, "that it's absolutely essential that we swap that."