Focus Part One: The science - Babymakers

The first test-tube baby was born 25 years ago this month. Since then thousands have become parents due to the miracle of assisted reproduction. But as scientists turn their dreams into our reality, we are becoming more and more uneasy about a future of designer babies and pregnant men. In the first of three special reports on the possibilities, pitfalls and dilemmas of the mother and father of all scientific debates, Steve Connor examines the future of babykind

Sunday 06 July 2003 00:00 BST
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Making babies was once such a simple affair. A candle-lit dinner, the scent of someone you love, and the rest could be left to nature. The problem for an increasing number of couples, however, is that nature can no longer be trusted to complete the cycle of life. More people than ever are turning to science to cure their childlessness. The trend for career women to start their families later in life and the problems of falling sperm counts in men have exacerbated the incidence of sub-fertility in Western societies.

For many couples, fertility treatment has become the last hope of realising their cherished dream of starting a family. Since the first test-tube baby was born 25 years ago, thousands of couples have become parents thanks to the technology of assisted reproduction - yet the science behind in vitro fertilisation (IVF) has generated disturbing questions about ethics and morality. Last week we became aware of just how bizarre this world of reproductive medicine can appear from outside the fertility clinics and research institutes. "Horror as docs take eggs from dead tots" ran one tabloid headline about a study to mature the eggs of 25-week-old aborted foetuses. "Now they want the eggs from aborted babies" was how another newspaper interpreted the research released at the European Society of Human Reproduction and Embryology in Madrid.

If ever there was a field of scientific endeavour so fraught with Promethean possibilities it is human reproduction and embryology. This is where the stuff of life itself is conceived, where the first sparks of human development are nurtured and the point where our precious genetic inheritance is passed from parents to children. The proto-scientist Victor Frankenstein was trying to breathe the same life force into his cadaverous creation.

Walking around the conference centre outside Madrid, there were no obvious Frankensteins among the delegates. Young researchers in T-shirts mingled with portly middle-aged men in Armani suits - the denizens of the private fertility clinics where the wealthy and the desperate are charged up to £10,000 for a single cycle of IVF treatment. This was the annual rendezvous for veiled female researchers from the Muslim world, for scientists and doctors from China and Africa, and the reproductive specialists from the wealthiest universities and research centres in Europe and the US.

One such scientist was an Israeli from the Meir Hospital-Sapir Medical Centre in Kfar Saba. Before a packed auditorium, Tal Biron-Shental, a trained gynaecologist, gave a bland presentation about her attempts at maturing ovarian follicles - the fluid-filled sacs where eggs develop - taken from seven aborted foetuses aged between 22 and 33 weeks. As she explained in her matter-of-fact manner: "The shortage of donated oocytes [eggs] has prompted suggestions of the putative use of oocytes from aborted foetuses."

The study involved bathing foetal ovarian tissue in hormones to mature the unripe follicles to a stage never previously reached in earlier experiments. The ultimate goal, Dr Biron-Shental said, was to mimic the natural maturity of eggs in the ovaries of an adult woman so that foetal eggs could be "farmed" in a test tube and supplied to infertile women lacking functional ovaries of their own.

"The local ethical committee of our medical centre approved the study and informed consent was obtained from the mothers," Dr Biron-Shental said. However, on closer questioning she had to admit that "there are a lot of ethical questions [and] we don't have all the answers for those ethical questions".

Supplying fully developed eggs from foetal ovaries raises the prospect of creating children whose biological mothers were never born. But, however strange the concept of "unborn mothers" is to the wider public, there are scientific reasons to pursue the idea, at least theoretically.

A principal cause of infertility is the inability of women to produce their own eggs. Every girl is born with her full complement of eggs and there is no natural way of regenerating those that are lost during her lifetime, unlike the sperm-making factories within testicles. This is why much research has centred on ways of preserving ovarian tissue outside the body in the hope that follicles could be stimulated in the test tube to produce viable eggs for IVF. Some doctors, such as Roger Gosden of the Jones Institute in Norfolk, Virginia, have experimented with the idea of removing ovarian tissue and replacing it after, say, a woman has undergone cancer treatment that would have otherwise have left her sterile.

It is a noble and justifiable idea and one that circumvents the ethical issues centred on using foetal material. Yet banking ovarian tissue for transplant later in life raises its own intriguing possibilities. Few would argue about the ethics of ovarian transplants for cancer patients, but what about young women who want to bank their ovaries until after they have established their careers? Some women might merely want to carry out the procedure to delay the menopause and prolong youthfulness, and why not?

Yet another idea is to create mature human eggs from other cells, such as skin tissue. This is called "haploidisation" and involves tinkering with the way a normal or "somatic" cell divides so that instead of retaining the full complement of 46 chromosomes (the diploid number), precisely half (the haploid number) are lost in the same way that they are ejected when "gametes", the eggs and sperm, are created within the ovaries and testes.

If scientists can create viable human eggs from skin cells then it would enable women lacking functional ovaries to have genetic babies. But it raises the prospect of generating eggs from the skin of men, allowing, for instance, a homosexual couple to be father and mother to their own genetic child.

Even male pregnancies are not such a far-fetched idea in the world of fertility research. Professor Mats Brannstrom, of Sahlgrenska University in Gothenburg, Sweden, has shown in experiments on mice that womb transplants are feasible. Mice who have been given wombs from other mice have given birth to healthy offspring, and Professor Brannstrom sees no reason why it should not be possible to carry out a similar procedure on women with no womb of their own.

He envisages womb transplants between relatives and friends, such as an older sister who has completed her family to a younger sister who cannot even start. It might even be possible to transplant a womb from a mother to a daughter so that the younger woman could bear a child in the same uterus in which she herself had developed.

"We know that a uterus from a 60-year-old woman can be as good as a womb from a younger woman," said Professor Brannstrom, who said there is nothing in theory to prevent a womb being transplanted into the abdominal cavity of a man. "Although I wouldn't do it," he added.

Fertility problems in men tend to be concentrated on abnormal sperm that cannot swim properly, or low sperm counts. The development of ICSI - intracytoplasmic sperm injection - has overcome many of the difficulties by taking individual sperm cells and inserting them directly into the human egg to by-pass the first stages of fertilisation. Normally, sperm and eggs fuse in a more controlled manner and the events that follow the point when a sperm powers its way through the thick, gelatinous coating of an unfertilised human egg is one of the most wondrous acts in biology.

Having penetrated the egg's outer shield, the head of the sperm fires out protein strands that act like harpoons, some of which anchor themselves to the egg's nucleus, dragging it towards the waiting head of the sperm, which is packed with the man's genetic information. A courtship of the chromosomes takes place during fertilisation, with the 23 pairs - one set from each parent - aligning in formation to produce the required 46 chromosomes of the fully fertilised egg. Shortly after this point is reached, the fertilised egg begins its cycle of cell division. It divides into two cells, then four, then eight and so on until a ball containing hundreds of cells appears less than a week after conception.

Precisely how a single, fertilised egg can become the trillions of specialised cells of a new-born baby is largely a mystery. What is known, however, is that up to a certain stage of embryological development, perhaps two, three or four days following fertilisation, each cell of the dividing embryo retains this ability to make a complete human being.

Taking one cell from a three-day-old embryo does not seem to affect its develop- ment - which is why scientists can test individual cells for genetic disorders as part of a pre-natal genetic diagnosis. It allows them to select embryos that do not carry harmful genetic traits. For others, however, the technique is just another step towards the creation of "designer babies".

Once again, a development in assisted reproduction can bring important advances in medicine. But like so many other developments in IVF, they can be used in more than one situation and what might be an acceptable use for some people, can be quite unacceptable for others. Making babies has never been so difficult.

Severino Antinori

Five years ago, the Italian fertility specialist announced plans to use cloning technology to help infertile couples. In 2001, the Italian medical authorities warned that he risked losing his right to practise in Italy because of his plans to clone humans.

Professor Ian Craft

Head of the London Fertility Clinic. In 1976, he became professor of obstetrics and gynaecology at the Royal Free Hospital School of Medicine. His team pioneered work resulting in the birth of Europe's first IVF twins on 29 April 1982.

Robert Winston

Professor of fertility studies at Imperial College School of Medicine. Lord Winston was part of the team that produced the first test-tube baby in 1978 and he founded the first NHS IVF programme. His techniques have been adopted worldwide.

Muhammed Taranissi

Director of the Assisted Reproduction and Gynaecology Centre in London, which has a licence to store women's eggs. He argues that the process could help women undergoing cancer treatment and career women to have children in later life.

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