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Fetuses Destined For Abortion May Be Used To Test Gene Therapy

New Scientist

CONTROVERSIAL plans to treat unborn children with gene therapy have been given an even more contentious twist. Under a proposal presented to a US government panel late last month, this therapy would initially be tested on fetuses destined for abortion.

Earlier this year, French Anderson of the University of Southern California in Los Angeles announced that he was seeking approval for fetal gene therapy (This Week, 27 June, p 12). He is still developing the techniques and will not be ready to start trials for at least three years. "We wanted to leave time for lots of public and private discussions," he says.

Anderson pioneered human gene therapy in 1990, when he treated children with a hereditary disorder called severe combined immune deficiency (SCID), caused by the lack of an enzyme vital for the development of the immune system. At a meeting of the National Institutes of Health Recombinant DNA Advisory Committee (RAC) on 24 September, Anderson described how fetuses with SCID would be given healthy copies of the gene for the enzyme. He also outlined plans for in utero treatment of an inherited blood disease called alpha-thalassaemia, caused by a defect in the gene for part of the oxygen-carrying molecule haemoglobin.

One concern is that a fetus's small size means the therapeutic gene has a greater chance of invading reproductive tissue and introducing genetic changes that will be passed down the generations.

But the committee had particular concerns about alpha-thalassaemia, says Claudia Mickleson, biosafety officer at the Massachusetts Institute of Technology and chair of the RAC. We each carry four copies of the gene that is defective in people with alpha-thalassaemia. In the worst cases all four copies are damaged and fetuses die in the womb or shortly after birth. The mother can also develop a life-threatening condition called pre-eclampsia, which involves high blood pressure and fluid retention. "If the therapy was inefficient, the fetus would still die, but its extended life span could increase the mother's risk," says Mickleson.

Anderson is now suggesting his team could get round this dilemma by asking women who had already decided to abort their fetus to take part in the first trial. Some RAC members agree that this avoids the ethical problems of a partial cure but, as Anderson admits, it has difficulties of its own. After aborting the fetus, the researchers might discover that they had managed to cure the condition. "The parents and researchers will have this guilt that I'm not sure it's possible to emotionally prepare for," says Anderson. The only solace, he says, is that the family would then be able to attempt another pregnancy knowing there was a treatment if the next fetus inherited the disorder.

At least one RAC member is deeply troubled by Anderson's proposal. Louise Markert, a paediatric immunologist at Duke University Medical Center in Durham, North Carolina, says: "Is it morally right to experiment on the fetus when it can give no consent and there is no way for it to benefit from the therapy?" Nevertheless, she applauds Anderson for having the courage to initiate such a controversial debate. "We're in the early stages and we'll visit these issues again and again," predicts Mickleson.

Author: Philip Cohen, San Francisco
New Scientist issue 10th October 1998, p.5



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