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The US National Institutes of Health (NIH) last week started what promises to be a prolonged and thorny discussion about the desirability of embarking on in utero gene therapy, a move that critics argue threatens to open up a “slippery slope to eugenics” (see Nature 395, 309; 1998).

After meeting for two days, NIH's Recombinant DNA Advisory Committee (RAC) announced a plan to set up four working groups to discuss various aspects of two newly proposed experiments, from informed consent — a clear difficulty when the subject is unborn — to issues of research design.

Following a broader ‘gene therapy policy conference’ on in utero therapy next January, the RAC will modify its guidelines, untouched since 1990, to address the issue.

The meeting focused on the dangers and merits of proposals brought to the RAC by W. French Anderson, professor of biochemistry and paediatrics at the University of Southern California, who has pioneered gene therapy in humans. Anderson and his collaborator, Esmail Zanjani of the University of Nevada School of Medicine, in Reno, are proposing two treatments for fetuses.

One treatment is for α-thalassaemia, an error of haemoglobin manufacture that in its severest form kills in the womb. Fetal blood would be withdrawn and incubated with a virus bearing the healthy form of the gene that otherwise causes production of abnormal haemoglobin. The cells would then be reinjected in the hope that they would produce normal haemoglobin.

The other treatment is for severe combined immunodeficiency (SCID), caused by a lack of the enzyme adenosine deaminase. Sufferers face immediate risk of succumbing to infection after birth. A retrovirus bearing the normal gene for adenosine deaminase would be injected into the peritoneal cavity of the developing fetus in the hope that it will be taken up by fetal immune-system cells.

Gene therapy in the fetus is thought to increase the chance of successful gene integration because cells divide much more rapidly than in adults. But it poses various risks, from altering germ cells to introducing harmful mutations in wrongly targeted cells.

A further risk is that the treatment would bring about only a partial cure, which some meeting participants argued could be worse for children with α-thalassaemia than if they had been left to die prenatally.

There are also concerns about risks of the therapies to mothers. For instance, toxic side effects to the mother in untreated α-thalassaemia are so severe that fetuses are aborted even before they die spontaneously. Some RAC members suggested that prolonging fetal life with experimental treatment may not be justifiable.

Anderson said he brought the proposals to RAC to raise “the issue of a potential inadvertent germline gene transfer”, among other risks. “If it is not possible to reduce those risks to an acceptable level [in the estimation of the Food and Drug Administration (FDA) and the NIH] we will not go forward,” he said.

Claudia Mickelson, chair of RAC and the biosafety officer at the Massachusetts Institute of Technology, emphasized that the proposals were taken up for “public discussion” purposes only.

But Amy Patterson, an FDA official who this month becomes director of NIH's Office of Recombinant DNA Activities, said that, once RAC develops its policy, the FDA would need a “very compelling” reason to ignore RAC's recommendations.