Science & Technology: Inconceivable?

Soon, it may be possible for any couple - gay, straight, infertile - to create a baby that carries both parents' genes. But, asks Steve Connor, is society ready for this?
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Imagine your street 20 years from now. Your kids may have grown up and left home, but who might be living next to you? It could be a young lesbian couple and their biological daughter - created when an egg of one of the women was fertilised with the synthetic sperm made from the skin cells of the other. The family on the other side may have a healthy boy, created in the test tube when sperm from the father was inserted into an artificial egg created from the skin of the mother.

This is not as far-fetched as it may seem. Scientists have already worked out how to make "artificial" germline cells - the vital precursors to sperm and eggs - in the laboratory. If they succeed, and the germline cells prove safe, the breakthrough could make infertility a thing of the past for any heterosexual couple who cannot have their own biological offspring even with the help of modern fertility treatments.

But the technique will break new ground by allowing same-sex couples to be both fathers and mothers to their own biological children. If healthy germline cells can be derived from ordinary skin cells, women and men will have the choice of producing both eggs and sperm.

At least three teams of researchers have demonstrated the plausibility of making synthetic germline cells, although they have so far only used laboratory mice. No one, however, has shown that these artificial sperm and eggs are capable of producing fertilised eggs that can develop into live offspring. But experts believe this is only a question of time; the important thing, they say, is that scientists now have a way of studying germline cells in the test tube. And it is this experimental model that has caused an explosion of interest in, and research into, the subject.

To understand the difficulties, it is necessary to understand a little basic biology. Sperm and eggs are fundamentally different from all other cells of the body in that they contain precisely half the usual number of chromosomes. In humans, this means that a sperm or an egg each carries just 23 chromosomes instead of the 46 carried by the other non-germline or "somatic" cells. Scientists refer to this number of chromosomes in sperm and eggs as the haploid number. The other somatic cells are said to contain the diploid number of chromosomes.

Normally, when somatic cells divide into two, the diploid number of chromosomes is preserved because each chromosome splits into two during the process of cell division. However, germline cells carry out an unusual form of cell division, meiosis, which halves the number of chromosomes in the resulting eggs and sperm. In human germline cells, the diploid number of 46 becomes the haploid number of 23.

The reason is simple. When an egg and sperm fuse to form a fertilised egg, the two haploid quotas of chromosomes unite and so double to become the normal diploid number, which is the hallmark of all somatic cells. The fertilised egg then goes on to divide in the usual way as part of the normal development of the embryo.

So, one of the first big barriers to producing artificial sperm and eggs is the process of "haploidisation" - getting a diploid cell to divide by meiosis to produce cells with the haploid number of chromosomes. Scientists have tackled this by culturing embryonic stem cells in the laboratory in such a way that they are induced into maturing or differentiating into germline cells that at some stage spontaneously divide by meiosis.

Hans Schoeler of the Max Planck Institute in Munster, Germany started the ball rolling in 2003 when he was a researcher at the University of Pennsylvania. Schoeler showed that he could make what appeared to be fully mature mouse eggs from stem cells taken from a mouse embryo. He found that when he bathed embryonic stem cells in a certain mixture of growth stimulants, it was possible to trigger their differentiation into eggs.

Although the eggs recruited other nearby cells in the culture dish to form follicle-like structures - just like those in a mammal's ovary - it has so far proved impossible to produce live offspring by fertilising these synthetic eggs with sperm cells. Nevertheless, the importance of Schoeler's work is that he has showed that it is indeed technically possible to produce eggs from embryonic stem cells.

We also know that it is possible to create embryonic stem cells by the process of cell nuclear transfer, the cloning technique used in the creation of Dolly the sheep. This is when the nucleus of a somatic cell - say, from the skin - is placed into an empty egg cell and then stimulated to divide into an early embryo as if it was a fertilised egg. Stem cells taken from such embryos are genetically identical to the individual who supplied the skin cell.

So, technically and theoretically, it should be feasible to create synthetic eggs, using the Schoeler method, by taking the skin cells of a man and manipulating them with the Dolly technique. All that is needed is a source of eggs from a female donor, which would have their own chromosomes removed. By inserting the nucleus of a man's skin cell into the empty egg and stimulating the cloned embryo to produce germline stem cells, it would allow that man to become the genetic or biological "mother" of his child - which would, of course, still have to be born to a surrogate mother. Technically, this is not reproductive cloning and so would not be banned under the present law.

The flip side is the creation of sperm by a similar process. At least two teams have made important strides here. Niels Geijsen of Harvard Medical School and Toshiaki Noce of the Mitsubishi Kagaku Institute of Life Science in Tokyo have manipulated embryonic germ cells to differentiate into sperm cells. Although these sperm lack functional tails, they appear to be genetically similar to true sperm and can, when injected directly into eggs, achieve fertilisation - although as yet neither group has announced the birth of live offspring resulting from such fertilisation.

The impetus for such work is primarily directed at allowing infertile heterosexual couples to achieve the dream of having their own biological children. Professor Alan Trounson, a fertility specialist at the Monash Institute of Reproduction and Development in Victoria, Australia, said two years ago that he believed the technique would cure infertility for everyone within a decade. "I'm certain that in the long term we'll be able to help everybody. At some time in the future, we'll be able to take cells and reconstruct the equivalent of sperm or the equivalent of eggs... In 10 years' time, I think we might think it's a rather good thing to do for someone who's had cancer and lost all their sperm or all their eggs," he said.

But the opportunity the technique provides to homosexual couples is already being raised by some ethicists and scientists. Giuseppe Testa, a fertility expert at Dresden University in Germany, and John Harris, an ethicist at Manchester University, have argued that the issues should be debated now rather than left until science has completed the necessary breakthroughs.

"Two men could potentially have a child to which both parents contribute their genomes, one through the natural process of spermatogenesis [sperm formation], the other through the assisted processes of genome programming down the female germline," they they wrote last year in the journal Science. "The possibility of an all-male or all-female couple's being able to have a child sharing the genetic make-up of both parents... is thought-provoking, and can be used as a lens through which to discern our attitudes towards parenting and family, as well as our notions of what is `natural'."

Thirty years ago, there were no children alive who had been conceived outside the body. Now there are millions of "test tube" babies, maybe even one living in your street. In another 30 years' time, the same might be true of babies conceived in same-sex unions.