A germ of an idea leads to GM people

Scientists are starting to contemplate the unthinkable: geneticengineering that would change the course of human evolution. Ayala Ochert reports

Genetically modified foods may be the big issue in Europe, but in the United States there is serious talk of genetically modified people. Scientists have begun to talk openly about the possibility - even the desirability - of taking direct control of our evolution through so-called "germline" gene therapy.

It has been almost ten years since four-year-old Ashanthi DeSilva became the first person to undergo "somatic" gene therapy. DeSilva, born with no immune system, would have had to live in an infection-free plastic chamber had she not received transfusions of the genes she lacked. But a line was drawn: only somatic cells, the cells of the body, were to be treated. Cells of the germline, sperm or eggs, were forbidden territory.

Gene therapy helped DeSilva, now a teenager, but last year it took the life of another young person, 18-year-old Jesse Gelsinger. He was the first person to die from gene therapy, which was being tested as a potential cure for his rare liver disease. It was a bitter blow to somatic gene therapy, which was already failing to fulfil its early promise. It had been predicted that by the turn of the century there would be cures for cystic fibrosis, sickle-cell anaemia, even some cancers, but progress has been very slow.

These setbacks to somatic therapy and developments in biotechnology recently prompted some in the US to begin to think the unthinkable - crossing the line into germline gene therapy. At a meeting organised by Gregory Stock of the University of California at Los Angeles, scientists talked candidly about their hope that techniques for human genetic modification would be developed within 20 years.

Germline modification is controversial because unlike the genetic content of somatic cells, which is lost when we die, the genes of germ cells are passed from generation to generation. Change the germline and you take control of evolution.

Prominent among the participants at Stock's meeting was James Watson, co-discoverer of DNA's structure and now president of Cold Spring Harbor Laboratory. He went much further than others in advocating germline modification. "If we could make better human beings by knowing how to add genes, why shouldn't we do it?" he asked. "Evolution can be just damn cruel. What we want to do is treat other people the way that maximises the common good of the human species. And that is about all we can do."

The American Association for the Advancement of Science has also been considering the technical, ethical and legal prospects of germline gene therapy. A group of scholars convened to discuss the issues held its final meeting last month. Though more conservative than the scientists at the UCLA meeting, they shared a consensus that there was nothing wrong with germline therapy in principle, but they felt that the barriers to it - regulatory and safety - were "formidable".

Theologian Ronald Cole-Turner, of the Pittsburgh Theological Seminary, admitted that many in the group were mystified by the widespread abhorrence to germline modification in Europe. Twenty-three countries have signed a Council of Europe declaration that specifically prohibits germline modification, considering it an affront to humanity. "We just could not see how germline modification affected human dignity," says Cole-Turner.

Stock believes that with new technologies making germline genetic engineering ever more feasible (see right), now is the time for public debate. "Human genetic engineering is not growing out of work that some crazy scientists are attempting in order to generate a master race. It is growing out of the mainstream of today's research: research in fertility clinics, in medicine, in biology and in pharmaceutical companies," he says.

Some scientists anticipate that germline therapy may be easier than somatic therapies because only one cell, the fertilised egg, needs to be modified, rather than the many millions altered in somatic gene therapy. But AAAS panel member Theodore Friedmann, a molecular geneticist at the University of California at San Diego, warns against such claims, as well as the idea that practical germline therapy will be ready soon. "If you learn how to do an efficient gene correction in the germline, then you are likely to be able to do it in somatic cells, too," he says.

Decisions concerning potential germline modifications are being made at the National Institutes of Health in Bethesda, Maryland. Its Recombinant DNA Advisory Committee was recently asked to consider a proposal for a gene therapy experiment that would carry a theoretical risk of inadvertent germline modification. The idea was put forward by French Anderson, the University of Southern California paediatrician who pioneered somatic gene therapy. He suggested that foetal gene therapy might help children such as DeSilva by treating them while they are still in the womb. But he acknowledges that genes injected directly into a foetus might find their way into germ cells.

Anderson opposes germline therapy for the foreseeable future. "We read about transgenic mice that have been developed, about Dolly, Polly and other cloned and transgenic livestock, and the impression is that it may be a simple step to go to germline genetic engineering in humans. This impression is incorrect - 95 to 99.9 per cent of all 'engineered' embryos are damaged, most of them lethally," Anderson cautions.

But what if safety requirements could be met? Members of the AAAS committee said they were still hard-pressed to come up with any medical justifications for germline therapy. "When you pursue it, there are very few life-threatening diseases that would need it," Cole-Turner says. Pre-implantation diagnosis already helps couples at risk of genetic disease to have healthy children of their own. Embryos may be screened at the eight-cell stage and "disease-free" ones selected for implantation into a mother's womb.

The AAAS committee came up with only one possible scenario justifying germline therapy: a couple, both with cystic fibrosis, who wanted children. Any embryo they conceived would have the disease, too, so pre-implantation diagnosis would be useless. The group did not find this scenario compelling.

It has been claimed that given the chance, perhaps 20 per cent of parents would genetically enhance their children: choosing to make them taller, resistant to disease or more intelligent. Some see it as a natural extension of the parental desire to help their children succeed. "I see no difference between a ban (on germline engineering) and a similar ban on parents sending their children to computer camps in the summer: both are intended to better children, both will be done most by people with money and both are not the business of government," argues philosopher Gregory Pence of the University of Alabama in Birmingham.

But Ruth Hubbard of the Massachusetts-based Council for Responsible Genetics disagrees: "As for the notion that we need germline interventions to 'enhance' the abilities we can in our children, people who cannot deal with the uncertainties implicit in having a child even before that child is gestated are in for trouble. Successful parenting requires that we be flexible enough to accept our children whoever they are," she says.

Even the assumption that parents have a right to make such decisions on behalf of their children is hotly debated. "Our genes do not belong to just ourselves. The gene pool belongs to all of society," Anderson says. Nevertheless some, such as Stock, see this technology as our destiny. "Evolution is being superseded by technology, and the timescale will be far more rapid. Humans are becoming objects of conscious design," he says.