Designing a dilemma

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By Nell Boyce AMONG some desperate parents in the US, the word is out: if you want to have a baby with a specific trait, one that’s unrelated to the health of the child, the person to contact is Mark Hughes, at Wayne State University in Detroit. A decade ago, Hughes helped pioneer the technology that allows embryos created through in vitro fertilisation (IVF) to be genetically tested before they’re implanted in the womb. The goal is to prevent genetic disease without putting parents through the emotional burden of terminating a pregnancy, but critics charge that choosing embryos could lead to parents making “designer babies”. But the parents desperate to contact Hughes aren’t interested in babies with blue eyes, high intelligence, or athletic prowess. In each case their first child is already sick with a genetic disease such as beta-thalassaemia or severe combined immunodeficiency syndrome (SCID). They want another baby that is not simply free from the inherited disorder but has a tissue HLA type that exactly matches the first child—a baby that could provide its sick sibling with a life-saving transplant. Is it too much to ask, while he’s testing the embryos for the disease gene, that Hughes also test the embryo’s HLA type? That way, they might have two healthy children. For years, Hughes refused. HLA type had nothing to do with the embryos’ future health, and he worried that this type of testing might provide a precedent for selecting embryos with genetic traits that the parents desired. Parents didn’t see it that way, as he vividly recalls. “While you’re sitting around mahogany tables debating this, my child is dying!” one furious father shouted. Now Hughes has decided he will do it, as long as the parents always intended to have a second baby and the tissue typing is just an add-on genetic test, rather than the raison d’être for the new child’s life. He’s done it for several families, and that’s the closest that preimplantation genetic diagnosis (PGD) has ever come to trait selection in his lab—a far cry from eugenics, he argues. It angers him that the press can’t seem to write about PGD without connecting it to “designer babies,” when the reality is so much different. “This is an incredibly complicated process that only people who are very desperate are going to bother with,” Hughes says. “People are not going to come at this for trivial reasons.” The technology needed to test for many diseases and traits such as eye colour remain a long way off, he adds. Unlike single-gene defects such as cystic fibrosis, these conditions are influenced by many genes, most of which have yet to be found. Critics, however, argue that this will change as IVF becomes cheaper and easier, and as geneticists unravel more of the human genome. Some scientists, such as William Gibbons of the Jones Institute for Reproductive Medicine in Virginia, think that our technical abilities are expanding so quickly that it would be wrong to dismiss the likelihood of such things happening in the near future. Now, Britain’s Human Fertilisation and Embryology Authority (HFEA), along with the Advisory Committee on Genetic Testing, have opened a public consultation on how the 10-year-old technology should be used. The HFEA is taking evidence until 31 March next year. “I’m glad they’ve finally gotten around to it,” says David King, editor of GenEthics News, who argued in the April issue of the Journal of Medical Ethics (vol 25, p 176) that PGD could usher in a new era of eugenics. To perform PGD, eggs are taken from the mother and fertilised just as in normal IVF. Before any growing embryos are implanted in the womb, however, researchers remove one or two cells using a fine glass needle. Various tests can be done on these cells, and if a genetic defect is found, parents can choose not to use the embryo from which the cells were taken. In a situation where both parents are carriers of the SCID gene, three out of four embryos will be healthy, while one in four embryos will be the correct HLA type. At the moment Hughes does not charge for any of his testing because he regards it as experimental work. The first published case of PGD appeared in 1990, when researchers at the Hammersmith Hospital in London reported the birth of twin girls. PGD had been used to select for female embryos in families with diseases caused by defects on the X chromosome (Nature, vol 344, p 768), which affect only male offspring. The Hammersmith researchers and Hughes then teamed up to test embryos for cystic fibrosis, and, two years later, they reported the birth of a healthy girl in The New England Journal of Medicine (vol 327, p 905). Now four centres in Britain are licensed to carry out PGD, and around 20 babies have been born using the procedure. In the US, testing is more widespread. Hughes says that on the basis of testing at his Wayne State University lab, 25 babies have been born around the US after PGD for Huntington’s disease alone. And Yury Verlinsky, director of the Reproductive Genetics Institute at the Illinois Masonic Medical Center in Chicago, estimates that over 200 children have been born following PGD at his institution. Even though the technology is currently limited to single gene defects and chromosomal analyses, researchers who work in preimplantation genetic testing have already come up against ethically dubious propositions. The most obvious is sex selection, and most labs refuse to use PGD for this purpose unless parents are trying to avoid disease linked to the X chromosome that affects male children. In 1993, the HFEA came out against sex selection for social rather than medical uses, and in the US the American Society for Reproductive Medicine made similar recommendations. But it’s highly likely that some companies will be willing to offer it. Another sticky issue is testing for late-onset diseases. This first came up four years ago, when researchers at Hammersmith Hospital revealed that they would test embryos for a gene that gives an 80 to 90 per cent chance of colon cancer (New Scientist, 28 October 1995, p 14). Other genes of interest to parents include the “breast cancer gene”, BRCA1, and the gene linked to Huntington’s disease. “I would screen for BRCA1. Why not?” asks Verlinsky. But someone who inherited a gene for a late-onset disease could have decades of healthy life—and perhaps never develop the disease. Besides, in twenty years’ time, it might be possible to prevent or cure such illnesses. Such hope, King argues, does not apply to devastating childhood disease that can be avoided by PGD, such as Tay-Sachs. Based on the public consultation, Britain’s HFEA may recommend that restrictions be placed on PGD testing for genes such as BRCA1. In the US, however, past experience suggests that reproductive technologies will be market driven. “The way that things are likely to go in the US is extremely worrying,” says King. He says that DNA chip technology may some day allow researchers to screen for thousands of different genes at once. In theory, Hughes says researchers could use a chip to test a single cell for multiple genes. But he adds: “The technology has got a long, long way to go before you could. All of the things that you might test for are polygenic [traits influenced by more than one gene]. We don’t even know what these genes are.” Hughes thinks that one argument against screening for many genes is that, unlike selecting for HLA-type or SCID, you would have so few embryos to choose from. The greater the number of genes, the rarer the desired embryo-type would be. However, given the pace at which genetic technology is advancing, Gibbons thinks it’s feasible that DNA chips might allow researchers to screen for conditions caused by more that one gene early in the next century. And if the tests are cheap enough, and researchers can identify genes associated with traits that preoccupy parents, King doesn’t see why using PGD to have “designer babies” should remain science fiction. “Pre-implantation diagnosis tends to kind of tilt the slippery slope,