Parliamentary debate continues on stem cells

By Graeme O'Neill
Thursday, 26 September, 2002

Behind the headlines, hype and huff-and-puff politics surrounding the therapeutic use of stem cells, there is fierce debate even among the experts over which research route holds the greater promise: adult, or embryonic?

One leading researcher testifying last week's Senate Community Affairs Legislation Committee hearing on Research Involving Embryos and Prohibition of Human Cloning Bill 2002, described embryonic stem-cell science as "passé", "incredibly boring" and "overhyped.

Prof Michael Good, director of the Queensland Medical Research Institute in Brisbane favours a third route: using chemicals or naturally occurring compounds in the body that stimulate existing stem cells in the body to repair or reconstruct damaged tissues or organs.

He described an overseas experiment in which male bone marrow cells grafted into female patients treated for leukaemia and lymphoma had subsequently differentiated into liver, gut and skin cells.

Good, an immunologist, pointed out that tissues or organs grown from grafted embryonic stem cells would be rejected in the same way as today's organ grafts, unless they were carefully matched to the recipient's own tissue type. Seven million people around the world were registered as potential bone marrow donors; the chances of someone of Caucasian ancestry finding a 'match' were 53 per cent, but for Asians, only 10 per cent, according to Good.

The same problem would apply to embryonic stem cells. Good said Prof Alan Trounson, director-designate of the new National Stem Cell Centre, had said that as few as dozen embryonic stem cells would be required, while South Australian biotech company BresaGen put the figure at 600 to 1,000 stem cell lines.

The real figure required to maximise the chances of tissue matching, said Good, was at least 10 million different cell lines, representing all the major racial groups.

"There seems to be an inordinate haste to rush into working with human embryonic stem cell lines when the proof-of-concept, or proof-of-principle, has not been established in animal systems," he said.

Good also questioned Trounson's assertion that adult stem cells lacked the genetic plasticity of embryonic stem cells, which could form any of the 200-odd different tissue types in the human body.

He said the greater plasticity of embryonic cells was actually a disadvantage -- it would be hazardous to introduce cells into patients that had the potential to transform into many unwanted cell types, and to form fast-growing cancers called teratomas.

Adult stem cells, with their limited transformation capacity, were the superior option, he said -- and had the advantage that if they were taken from the patients themselves, there would be no rejection problem.

Prof Paul Simmons, of the Peter MacCallum Cancer Institute, said he was a "passionate believer" in the potential of adult stem cells, but called for a balanced research program into both embryonic and adult stem cells.

Adult stem cells with the capacity to form specific organs were elusive -- there had been some progress on liver stem cells, but stem cells capable of repairing major organs like the heart, lung and kidney, or in diabetics, the pancreas -- had not yet been identified, he said.

The fact that such cells were rare would make it difficult to isolate them in the numbers required for effective therapy. Some adult stem cells would not multiply in tissue culture systems.

Simmons said some adult stem cells did not appear to have the plasticity initially claimed for them, so the plasticity of adult stem cells should not be used as an argument against the use of embryonic stem cells.

Prof Perry Bartlett, of the Walter and Eliza Hall Medical Research Institute in Melbourne, told senators that his research team had purified a population of brain stem cells that had the capacity to form new neurons, raising the possibility that brains damaged by Alzheimer's or Parkinson's disease, or by stroke, could be repaired.

He said an overseas research team had recently shown that brain stem cells could form new neurons in the hippocampus, a brain centre involved in the formation of memories.

They had shown that monkeys suffering stroke damage to the hippocampus had not only regrown lost neurons, but had actually performed better in memory tests involving mazes.

He agreed with Good that the simplest way to repair tissues was to activate n-situ stem cells; the challenge was to identify the compounds that the body used to activate stem cells, and understand how they worked.

Bartlett said embryonic stem cells would be difficult to integrate into damaged brain tissues; inducing the cells to differentiate into the right cells was one problem, but their tendency to form teratomas was "a major stumbling block".

Prof Peter Rowe, a stem-cell expert with Sydney's Westmead Children's Hospital also said adult stem cells were the superior option -- "To me, at this stage, embryonic stem cells have very little to offer."

He said Alzheimer's and Parkinson's diseases, and diabetes, were very complex disorders.

"To say that you will cure them by putting in a few cells is a joke," he said. "We know that Alzheimer's is a global disease; what are you going to do -- replace the brain?"

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