Screening the next generation

A new procedure means embryos can be checked for 4000 diseases. Picture / Daily Post

PRAGUE - Thousands of women at risk of giving birth to sick children could benefit from a revolutionary technique to ensure that their babies are free of genetic disorders.

Five women in Britain are pregnant after having their embryos screened by the technique, which can screen out the genes for disorders such as cystic fibrosis and Duchenne muscular dystrophy.

The gene for cystic fibrosis is carried by one in 25 Britons and affects 7500 children. Duchenne muscular dystrophy affects one in every 3500 male births. These are just two of more than 4000 single-gene disorders that could be identified by the technique.

It is the first time that "test-tube" embryos have been identified and selected by a new medical procedure hailed by its inventors as a "paradigm shift" in the screening of defective genes.

The pregnant women are all carriers of genetic disorders and have opted for the experimental test in the hope of having healthy, unaffected babies following in-vitro fertilisation (IVF).

For about 10 years it has been possible to test IVF embryos for certain genetic diseases in order to implant only healthy embryos, but this method of pre-implantation genetic diagnosis (PGD) has limitations, according to experts.

The latest procedure is more accurate, more powerful and marks a radical development in the technology of testing embryos, said Peter Braude, professor of obstetrics and gynaecology at King's College London.

"We really think this is a big, big change in terms of what we usually do. This changes everything, it really does," said Professor Braude, a scientific adviser to the Human Fertilisation and Embryology Authority.

PGD involves taking a single cell from an IVF embryo and delicately testing the minute quantities of DNA it contains for the presence of a known mutation for genetic disorders such as cystic fibrosis.

The new procedure, called pre-implantation genetic haplotyping (PGH), takes a single cell and multiplies its entire genetic complement a million-fold before testing whether the embryo has inherited the defective part of a chromosome from its father or mother.

"We don't have to know the precise details of the genetic mutation and it just opens doors to all sorts of disorders," Professor Braude said.

"It improves dramatically the diagnostic success rate because you can make the diagnosis more reliably and you have more embryos at the end of it. It's more accurate, it has a higher reliability, it's going to be available for a whole range of disorders," said Professor Braude, who announced the breakthrough at the European Society of Human Reproduction and Embryology in Prague.

Two of the five pregnant women tested by PGH are carriers of the defective gene for Duchenne muscular dystrophy, two carry mutations for cystic fibrosis and the fifth suffers from a rare condition that can result in cancerous tumours during pregnancy.

Duchenne's disease affects boys, who inherit it from mothers who carry a genetic mutation. The women themselves are healthy and unaffected. At present, couples who want an unaffected child are offered prenatal sex testing and a termination if the foetus is male. Another alternative is sex selection of IVF embryos to implant only females - this leads to the deliberate destruction of male embryos, even though only half are at risk of Duchenne's.

PGH can identify the 50 per cent of male embryos that will be unaffected, said Alison Lashwood, a consultant nurse at Guy's and St Thomas' hospitals in London.

"We can tell the difference between the affected and the unaffected males and that, for some couples, will make a difference between whether they get an embryo transfer or not," Ms Lashwood said. "At least using this technology we are hopefully increasing the number of embryos, and we'll help some people to achieve pregnancy," she said.

Pam Renwick, the geneticist at Guy's Hospital who has pioneered development of the test, said that the technique could be applied to any genetic disease where the mutation had been located on a region of a particular chromosome. "It's a universal test ... it has the added advantage that we can now select for unaffected males, which increases the number of embryos for transfer into the womb," Dr Renwick said.

The PGH test can also distinguish between female embryos that are healthy carriers of a defective gene from those that are completely free, non-carriers.

This raises the ethical issue of whether to offer couples the opportunity to discard female embryos that are healthy carriers in favour of healthy non-carriers. Some couples have already asked whether it is possible to use genetic tests to choose non-carrier embryos, even though carrier female embryos would lead normal, healthy lives - like their mothers.

"We've not actually taken anyone through who has asked for that at this stage," said Ms Lashwood.

"At the end of the day, we are aiming for couples to take home a baby." Professor Braude said: "If you are looking at the eugenic implications of saying that we're trying to eliminate a disease from a family, that's a completely different story from what we are trying to do," he said. "This is nothing to do with screening. This is to do with families at significant risk who can choose this technique over prenatal diagnosis and termination of pregnancy."

- INDEPENDENT