washington

A conference on in utero gene therapy organized by the US National Institutes of Health (NIH) concluded last week that many significant scientific and ethical questions must be answered before the practice can or should be attempted in humans.

But despite the obstacles — and determined opposition from activists who attended — senior NIH officials said they would continue to revise their guidelines on gene therapy to address eventual in utero applications. The revisions could be published as soon as June.

The Food and Drug Administration (FDA), which holds the final power to approve in utero protocols, also appeared keen to push ahead. “We need to make sure that whatever we do, the very best technology is used,” Philip Noguchi, director of the FDA's Division of Cellular and Gene Therapies, told the meeting. “And the only way to get there is to really force the issue.”

The technique's immaturity was clear at the meeting. Experts pointed to a dearth of animal data, and to human risks including inadvertent genetic modification of fetal sperm and eggs, or even of the rapidly proliferating breast and uterine tissue of mothers.

Some also warned of children being only partially cured of severe diseases, and posing formidable, lifelong costs to their families and the healthcare system. And others pointed out that, even in adults, gene therapy has not succeeded.

“I don't know how we can talk about selling it in utero ,” said Mitchell Globus, professor emeritus of obstetrics and paediatrics at the University of California, San Francisco, and the director of scientific and clinical affairs for Applied Imaging Corp. “We don't have a product to sell post-natally yet.”

Despite this, many of those present agreed that the impetus to attempt therapy, despite the risks, is compelling for severe diseases that kill before or shortly after birth, and for seriously disabling diseases with no adequate treatments.

“There is a consensus that in utero gene therapy will have a definitive role to play in a small set of diseases,” said French Anderson, professor of biochemistry and paediatrics at the University of Southern California, and a leading pioneer of human gene therapy.

While some at the two-day conference complained of the lack of animal data, there were also signs of progress with animal experiments. Janet Larson, for instance, a neonatologist and staff scientist at the Alton Ochsner Medical Foundation in New Orleans, Louisana, described the successful treatment of cystic fibrosis in knockout mice with in utero therapy.

Meanwhile, Anderson is preparing human protocols for using in utero gene therapy to treat severe combined immunodeficiency and α-thalassaemia. He estimates that they will be ready for submission as soon as three years from now. But he is now modifying the draft proposals after questions were raised by the NIH's Recombinant DNA Advisory Committee last September (see Nature 395, 420; 1998).

Activists at the meeting, led by the Council for Responsible Genetics (CRG), argued that if the US government allows the development of in utero gene transfer to fight disease, the technique will inevitably end up being exploited for eugenic purposes.

Paul Billings of the CRG, a medical geneticist who is chief medical officer at Heart of Texas Veterans Health Care System in Dallas, blamed “genetic hysteria” for the meeting participants' openness to developing in utero techniques.

“The Council for Responsible Genetics questions why we're investing so much time and effort in gene therapy for very rare conditions when prenatal diagnosis, embryo selection and adoption are available,” said Billings. He and others also argued that, by providing therapy to younger and younger fetuses, scientists risk playing into an anti-abortion agenda by giving an earlier definition of the beginning of life.