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Baby who launched a test tube revolution

Louise Brown, the first test tube child, is 21 this year . . . and her story suggests that cloning is inevitable. Roger Highfield reports from London

Louise Brown was born 21 years ago. When she was conceived in a laboratory, she helped to launch a revolution in reproductive medicine that is still changing the world, challenging moral values and stirring religious debate.

Half a million test-tube babies later, her story remains extraordinary for the insights it gives into the relationship between society and science, when the despair of childless couples met the ambition and scientific curiosity of doctors.

Her story also underlines how medical research is a human enterprise, one that depends on perseverance and luck as much as hard science and animal experimentation. It will be told in full next month by award winning programme maker Eamonn Matthews in Britain's Channel Four TV series, The Baby Makers.

There are many echoes in the current debate over cloning. If we have learnt anything from Louise, it is that the revulsion that greets cloning is likely to give way to qualified acceptance when the public becomes aware of the benefits, such as the ability to grow tissue or clone infertile women.

The same will probably go for the brave new world of genetic enhancement. And if ``designer babies'' ever appear, it will be possible in part because of In Vitro Fertilisation (IVF), the technique that enabled Louise to be born.

Before she was conceived, human reproduction was regarded as almost sacred. Dr Robert Edwards, who helped bring her into the world, said it seemed to be a matter ``for theologians, rather than gynaecologists and scientists''.

Louise's mother and father, Lesley and John, were infertility statistics, the one couple in eight in Britain who could not have children. For 15 years, their family doctor had encouraged them to keep trying. ``But we never gave up hope,'' said John.

IVF began with Dr Edwards, of Cambridge, who was keen to extend work on animals to treat women with blocked Fallopian tubes, which prevent eggs from travelling from the ovaries to the womb, where they can be fertilised.

``It struck me what we should be trying to do was pluck the egg from the ovary and fertilise it in the laboratory,'' he said. ``We could do this in animals increasingly. This was the way to go in the human species.''

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Thirty years ago, this was heresy. Doctors thought IVF was science fiction, a dangerous idea driven by an appetite for headlines rather than scientific curiosity.

But Edwards had spent a decade on the problem. He had prepared eggs for fertilisation in several animal species and by 1965, thanks to work with Howard and Georgeanna Jones, Baltimore gynaecologists, he had transferred these techniques to humans.

And for those who had to deal with infertility, there seemed little to lose. Molly Rose, a gynaecologist, agreed to supply Edwards with ovarian tissue.

Early attempts to fertilise eggs from ovarian tissue using his own sperm proved fruitless. Then, one afternoon in 1969, he tested a culture medium supplied by a young student, Barry Bavister, who was working down the corridor.

After dinner, they returned to the laboratory and inspected the medium for eggs with a protruding sperm tail. Edwards could not find anything until half way through the nine eggs. ``I focused up and down and bang, a sperm tail,'' said Bavister. ``It was a stunning moment.''

Edwards described how, ``in that fabulous night we saw all of the most beautiful stages of human fertilisation, from about six hours to 12 hours after fertilisation''.

When news of their achievement spread, their peers were hostile.

Some scientists warned that any attempt to return the embryos to a woman could result in damaged children.

Edwards soon found that immature eggs, extracted from ovaries, would not develop for long. Here the other IVF pioneer entered the story. Patrick Steptoe, a gynaecologist in northern England, was routinely encountering ripe eggs in his work on laparoscopy (keyhole surgery).

They met at the Royal Society of Medicine, where Edwards was lecturing, and made the historic decision to collaborate. Working together, they gave patients small doses of hormones to produce more than one ripe egg, working out the best time to harvest eggs for fertilisation.

The embryos ``grew beautifully'' for up to three days. But Edwards was keen to reach the five-day stage, when the embryo is a so-called blastocyst and is ready to implant in the womb.

One night, after returning from Oldham, he saw four embryos in culture which seemed to be perfect blastocysts: human blastocysts for the first time ever. He invited a colleague doing similar work on mice to take a look.

``This did not look like a typical blastocyst,'' said the colleague. ``It dawned on me that he had just come back from Oldham. I said, `Is it human?' And he said, `Yes, this is our first blastocyst'. We just looked at each other and were extraordinarily silent.''

The time had come to move from the laboratory to the clinic. Steptoe began to recruit infertile couples to a cottage hospital outside Oldham. One of the nurses recalled that when an egg was removed the mood was electric, full of anticipation. Half the eggs developed into embryos. But a few days after implant, the attempt would fail and the women were sent home. One of the nurses recalls the tears and shouting.

By 1977, Edwards and Steptoe had endured five years of failure. Again, they looked at the cocktail of drugs used to stimulate egg production. They decided to abandon these and put their faith in the less productive natural cycle.

At that time, Lesley and John Brown were desperate. Inspired by the first heart transplant, they felt sure there must be an operation to fix a blocked Fallopian tube. She was referred to Steptoe, who met them in his rundown consulting rooms in Oldham, Manchester.

He declared them ideal candidates for IVF. ``He told us that until then it hadn't worked,'' said Lesley, ``but I didn't want to hear that.'' She reluctantly signed papers agreeing to an abortion if IVF deformed the foetus.

Steptoe and his team searched for a single egg when they made a renewed attempt, this time without the drugs, on Lesley and two other women in November 1977. ``They found one solitary egg and that was Louise,'' she said.

Her husband, John, was invited to make his contribution to fertilise the egg. ``I can always give you a hand,'' joked the nurse. ``No thank you,'' was his response. ``I went into a quiet room, did my little bit.''

By this time, Steptoe and Edwards had decided to halve the period that the embryo was grown in the laboratory. Louise consisted of just eight cells when Steptoe transferred her to Lesley Brown. ``I was just so positive it was going to work,'' said Lesley. ``I've never been surer of anything in my life.''

She wept when she received the ``very encouraging'' results of blood tests before Christmas. John ``went ballistic ... we went mad, hugging and kissing''.

Then came the confirmation, when the doctors listened to her swelling stomach and a nurse recalled ``you could hear a pin drop''. There, loud and clear, was a heart beat.

The pregnancy caused a sensation. ``We didn't realise we were the first, not until it actually came out in the papers,'' said John. He resented being doorstepped by the media. Lesley resented the journalese for IVF ``test-tube baby''. ``I just felt very, very insulted for the baby.''

In July 1978, her blood pressure spiralled, due to toxaemia, and Steptoe became anxious. On July 25, he decided to wait no longer. He left work early to wrongfoot the press, telling his theatre sister to prepare for a Caesarian just before midnight.

Lesley was readied under torchlight, so journalists outside the building would not see her room light up.

That night, at the culmination of years of slog to develop IVF, Steptoe and his team realised the stakes were high. ``I was very apprehensive,'' said Dr John Webster, assisting. ``If she had any abnormality, that would have been put down to the technique and it would have been very difficult to defend.'' He crossed his fingers as Steptoe made the first incision.

``Within five seconds of birth she let out the biggest yell you've heard a baby make,'' said Edwards. ``Patrick shouted, `That's what I like to hear, good lung development'.''

Steptoe recalled how Lesley was speechless when she first held Louise. ``The expression on her face was absolutely extraordinary.'' After a minute, she thanked him.

At first, John Brown refused to hold Louise. He was shaking too much, on what he now calls the most beautiful day of his life. ``Her little face, her eyes and her squawking. From the day she was born, she's never stopped squawking. She's a credit to us. A real credit.''

Within hours, the story of Louise was worldwide news. Steptoe and Edwards, after two failures, managed to produce the second child, Alastair Montgomery. And the Browns had another IVF child, Natalie. ``If it was wrong, God wouldn't have given Mr Steptoe or Dr Edwards the ability to do this work,'' said John Brown.

New techniques such as ICSI, when a sperm is injected into an egg, or the ability to grow human sperm in animals, give hope to men with a low sperm count. Pre-implantation genetic diagnosis and methods to sort sperm give new hope to carriers of genetic diseases.

Each advance is fundamental, said Edwards. ``They change an attitude. They change a way of doing things. They change an ethic. They change the way a nation looks at itself.''

(Daily Telegraph, London)

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