MEDICAL SCIENCE: by Babette FrancisNews Weekly
Embryo stem-cell research - hype and hope
, November 19, 2005
The Federal Government is once again facing increasing pressure to repeal laws banning human cloning and restricting experimentation on human embryos, writes Babette Francis. The Lockhart Committee, which is currently reviewing the 2002 federal legislation banning human cloning and restricted research on embryos, has indicated that it does not wish "to revisit the underpinning community debate and rationale for the  legislation".
One wonders why not, particularly as the committee is required to note "any changes in community understanding or standards".
Scientific research - especially in the medical area - moves so fast that many procedures on the "cutting edge" in 2002 may no longer be the most effective in 2005.
The committee is clearly keen to hear from academic institutions and potential beneficiaries of cloning and embryo stem-cell therapies, groups representing diabetics or sufferers of motor-neurone disease; but is probably less enthusiastic to hear from the people who insist that the end does not justify the means, and that neither cloning nor destructive research on embryos should be permitted, no matter how noble the ultimate objective.Con trick
It is to be hoped that people are finally waking up to the fact they may have been at the receiving end of a con trick, the great embryo stem-cell hype.
Using adult stem-cells, there are about 68 clinical trials or successful treatments for a range of ailments, ranging from blood disorders and heart disease to spinal cord and eye injuries. These stem cells are derived from ethical sources such as cord blood, bone marrow, muscle, fat and other body tissues (collectively known as adult stem-cells) and none
from embryonic stem-cells (ESCs).
Yet we are periodically subjected to Hollywood hype, with actors, such as Michael J. Fox (a Parkinson's disease sufferer), Mary Tyler Moore (severe diabetes), the late Christopher Reeve (paralysed in a riding accident in 1995) and others, pleading that scientists be given a free hand to slice up embryos for their stem cells so that the disabled might be cured of their illnesses.
What is significant is that even the scientists in favour of extracting stem cells from embryos (a procedure which kills the embryo), are starting to acknowledge publicly that there are serious problems in trying to harness ESCs.
At a Research and Learning Expo, organised by the Smart Geelong Network in August of this year in Geelong, Victoria, Barwon Health presented a "Great Stem Cell Debate".
Speakers included Professor Mark Kirkland, director of the Douglas Hocking Research Institute; Martin Pera, research professor at Monash University; and Dr Mark Manolopoulos, a doctor of theology at Monash University.
Professor Kirkland said he did not wish to rule out making or studying embryonic stem-cell lines because "embryonic stem-cells are fascinating, with enormous potential to improve our understand of cell biology, cellular differentiation and disease states; but the issue which needs to be addressed ... and in which there is truly a divide between embryonic and adult stem-cells, is in applied science and medicine".Clinical therapies
He asked: "Which form of stem cells can, and perhaps more importantly should, become the focus for developing clinical therapies for heart attacks, stroke, spinal cord injury, diabetes and many other diseases?"
He said: "The contention I wish to place before you is as follows: embryonic stem-cell therapies will not be a viable and generally available option for at least another 10 years and, by the time that such therapies are available, they will have been supplanted by cellular therapies based on adult stem cells."
He went on to mention one of the problems associated with ESCs - their propensity to form tumours when injected into patients.
"I am not saying that we should not be working on embryonic stem cells," he said.
"I am saying there is a huge gap between exciting results in the laboratory and even in animal models, and the development of safe and reliable treatments for humans - 'safe' and 'reliable' being the key words.
"This gap between laboratory promise and clinical reality has been seen time and again, and no amount of hype and no amount of venture capital, can deny the lesson to be learned from previous 'silver bullets' that have failed to live up to expectations."
While Professor Kirkland emphasised the tendency of ESCs to cause tumours when used in treatments, reports in New Scientist
and Human Genetics
indicate that ESCs may be inherently unstable and that this discovery may end hopes of using them in therapeutic applications.
A researcher from Johns Hopkins University - an institution that has backed the use of embryos for research - has found that ESCs that are cultivated in the laboratory accumulate genetic changes that may be linked to cancer.Mutations
"Like a genetic game of 'telephone', the longer the cells are cultivated, the more the genetic errors grow," warns geneticist Dr Aravinda Chakravarti at the university's Institute of Genetic Medicine. "These mutations we are finding are a much bigger problem."
Chakravarti's research team found that stem-cell lines, as they were cultured, went through 35 cell divisions and that 90 per cent of them showed changes in patterns of methylation - the process in which certain genes in a cell are turned on or off.
Some 22 per cent had mutations in mitochondrial DNA and 50 per cent had major deletions or amplifications in the DNA. Most worrying was the connection between the particular genetic problems the cells developed and the formation of tumours.
"If it turns out these cells really do become unstable over time," says Chakravarti, "then that would put limits on the practical life spans of the cells and their usefulness for therapeutic purposes."
Chakravarti has told New Scientist
that a possible solution would be to use the cells only when they are new and before they have undergone extensive cultivation and division.
However, the use of ESCs for treatment depends upon a long process of cultivation and differentiation into particular tissue types. Chakravarti's discovery may end any lingering hopes of using ESCs directly in therapeutic applications.
This discovery of the degradation of the genome of cultivated stem-cells comes at the same time as one of Britain's leading fertility experts decried the hype surrounding ESCs.
Speaking on the eve of this year's British Association's Festival of Science in Dublin, Ireland, Lord Robert Winston - professor of fertility studies at Imperial College School of Medicine, London University, and host of several television series, including The Human Body
- said the business of science is not certainty but uncertainty.
He cautioned: "I think we need to be considerably more modest about our science. We do tend to hype up so many activities. The latest one in biology is the issue of embryonic stem cells. I view the current wave of optimism about ESCs with growing suspicion."
Professor Lord Winston pointed out, just when John Hopkins University was publicising its discovery of the risk of stem-cell mutations, that one of the biggest problems with ESCs was that "cultured stem cells are inherently unstable. When grown in the laboratory, they often produced cells with chromosomal abnormalities".
While the hype surrounding ESCs is being discredited, new hope has emerged from the recent discovery of embryonic-like stem-cells in the lining of a baby's umbilical cord. These are called "cord-blood-derived embryonic-like stem cells" (CBEs).
CBEs are showing most of the versatility of ESCs without the drawbacks of the latter. When I raised this point with Professor Martin Pera at the Geelong stem-cell debate, he said he would be happy if it turned out to be true "because I could do without the aggravation" - aggravation presumably caused by pro-life activists who insist that it is wrong to slice up embryos.
When I cited the pioneering work of Professor Alan Mackay-Sim of Griffith University who derived stem cells from nasal tissue and showed that these adult stem-cells (ASCs) showed much of the potential of ESCs, Pera dismissed the findings with the words: "That's Cardinal Pell's opinion - I don't think the researchers are claiming that."
Whatever the limitations of ASCs, the key may lie in "reprogramming". It has been recently discovered that stem cells from skin can be reprogrammed so that they function like embryonic stem-cells, but without the risk of forming tumours.
Ethicist Mark Manolopoulos acknowledged that an embryo was a human being, but said that experimentation on embryos was permissible and could be likened to small-"m" murder because the principal motive was not to kill but was inspired by the noble motive of curing diseases.
He said, however, that such research should be funded only by the private sector.No excuse
My view is that, just because excess IVF embryos are destined to be discarded and die anyway, this is no excuse for experimenting on them.
The notorious Nazi, Dr Josef Mengele, no doubt thought that Jewish children in the death camps were going to die so he might as well use them for research for the benefit of mankind - or for the Aryan section of mankind anyway.
Jewish and Christian ethicists have maintained that whatever "useful" information Dr Mengele obtained from his cruel experiments should not be utilised.
We should feel the same about human embryos.
They may indeed be "fascinating" as Professor Kirkland said, but we should think about them as a wonder of God's creation, not to be killed for man's base purposes.
- Babette Francis, B.Sc (Hons), is co-ordinator of Endeavour Forum Inc.