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created from constructing an egg out of material from one mature egg and one immature egg, the equivalent of synthetic fertilization. Admittedly, Kaguya, like Dolly the Sheep before it, won a bit of a reproductive lottery. Out of the 371 reconstructed eggs that were implanted, only ten live embryos reached maturity, and only two survived outside the womb; Kaguya’s sister was killed so that the genes involved could be studied in more detail. But within just three years, the scientists had honed the technology to produce fatherless mice that develop at a high success rate – equivalent, in fact, to the rate obtained with in vitro fertilization of normal embryos. Like Kaguya, these new generations of mice – all female, of course, since they only have sex chromosomes from eggs – have proved able to reproduce with males and produce fertile offspring.

To achieve this, Kono’s team deleted two bits of DNA, called H19 and Dlk1-Dio3, which are imprinted in the mother but also serve as key controllers of imprinting across the genome. The first imprinted gene to be identified, IGF2, is imprinted in the mother, and so is expressed in the child from the father’s copy. What was particularly striking is that a substantial number of genes that have subsequently been discovered to be imprinted act as part of a pathway in which insulin-like growth factor-2 is crucial – the very thing that IGF2 codes for. And one of these genes is H19.

The other critical imprinted region, Dlk1-Dio3, contains genes that encode proteins expressed only when they come from the father. The genes in the Dlk1-Dio3 area are found throughout the embryo, but after birth, they are predominantly located in the brain, where their instructions for constructing the tiny pieces of machinery that regulate the workings of other genes do their work. These instructions are expressed only from the chromosome inherited from the mother. Some switch had to be turned, in order for the father’s gene to stop influencing the offspring.

It was H19 and Dlk1-Dio3 that Kono and his team deleted to make Kaguya the mouse. Tampering with these sections effectively allowed them to use the egg’s chromosomes as though they had come from a sperm.

Making human babies using Kaguya-style genetic tinkering should be possible in the future. But doing so will yield only female offspring, unless we can get hold of a Y chromosome, even one manufactured in a lab. In 2007, a first step in this direction was taken: in a painstaking process, a synthetic chromosome was assembled using lab-made chemicals – that is, copies of the chemicals that make up DNA. The artificial chromosome contained 381 genes containing 582,970 base pairs – paired letters of the DNA alphabet. The pioneering biologist behind this construction was Dr Craig Venter, whose company, Celera Genomics, helped to unravel the sequence of the human genome, in parallel with the government-backed Human Genome Project, in 2003.

The initial design of Venter’s artificial chromosome was based on a parasitic bacterium called Mycoplasma genitalium, which is considered the smallest naturally occurring genome in cell form. Venter’s team extracted the bacterium’s own DNA and inserted the synthetic reconstruction in its place. When they finally succeeded, they branded the creation as the first truly new artificial life form on earth. In Venter’s words, the artificial chromosome was ‘a very important philosophical step in the history of our species. We are going from reading our genetic code to the ability to write it.’ Learning to write genetic code will be more complicated when it comes to creating artificial eggs and sperm, especially on the scale of Homo sapiens’ twenty-three thousand genes, even after taking account of the ‘non-coding’ portions of the genome.

Still, the ability to create artificial eggs and sperm from stem cells is hailed as the technology that will finally bring an end to infertility. And rightly so, as it will also help us to uncover many of the remaining secrets surrounding how reproduction works. Experiments to make artificial eggs and sperm are likely to yield an increased understanding of genetic imprinting and the diseases that arise when imprinting goes awry. Since the cells that become the placenta can also be derived from these stem cells, this research could allow scientists to investigate how the early placenta develops and how disorders arise in it. And of course, artificial germ cells would allow individuals to bypass donors, avoiding the ethical issues of the egg and sperm trade. In fact, because the children produced from these cells will not be ‘artificial’ babies, scientists prefer to call them in vitro-derived cells.

In vitro-derived cells should be able to withstand freezing and be stored for future use, just as their ‘natural’ donated counterparts already are. The freezing procedures used today are much the same as they were in the early 1950s, when the modern technique was established. Scientists had been able to freeze and store sperm by the 1930s, but had not found a way to ensure that the sperm were not damaged, rendering them useless for reproduction. In 1949, two British scientists, C. Folge and A. D. Smith, were part of a team who finally succeeded in ‘reviving’ sperm after preservation, by using glycerol to maintain the sperm’s structural integrity as it is plunged into temperatures around minus 196 degrees Celsius (minus 320 degrees F), and the process was improved substantially a few years later by the ‘father of cryobiology’, American zoologist Jerome K. Sherman. UK law currently only allows sperm frozen in this way to be kept for ten years, but as there is no evidence of any changes in quality over time, in theory, sperm suspended like this can last forever – no matter the source of the sperm.

Things are not as straightforward, however, when it comes to freezing eggs. Unlike sperm, which are quite small, the