Like a Virgin (16 page)

A complete human is built from the instructions spelled out on our forty-six chromosomes. Twenty-three of these we inherit from our mother’s egg, and twenty-three from our
father’s sperm. The egg and the sperm, unlike every other cell in the human body (except red blood cells, which contain no chromosomal DNA), therefore each have only twenty-three chromosomes.
When egg and sperm fuse during fertilization, these chromosomes are paired – say, chromosome 15 from your mother’s egg will be matched with chromosome 15 from your father’s sperm
– and form a full double-helix set of forty-six chromosomes in the resulting cells.

If you were then to compare the genes on these two sets of chromosomes, you would find that they are either
homozygous
(encoding the same instructions) or
heterozygous
(encoding different instructions) for certain genes that lead to a child’s inheritance. Take
EYCL3
, one of the genes that spell out the colour of your eyes.
EYCL3
is located on chromosome 15 and codes for either a blue or brown tint in the iris. The chromosomes 15 that you inherited from your mother and your father may both carry the blue
variant of the gene, in which case you are homozygous for this gene and are likely to have been born with blue eyes. On the other hand, the chromosome 15 you inherited from your father may encode
brown eye colour, and the one from your mother may encode blue eye colour, and in this case, you are heterozygous for the
EYCL3
gene and will probably have brown eyes. (The inheritance of
eye colour is quite a bit more complex than that, involving several genes and their interactions.)

By this logic, the DNA of ovarian teratomas, coming only from an egg, should be homozygous – it all comes from the mother, after all. But some genes in mature ovarian teratomas have been
found to be heterozygous. And teratomas almost always contain forty-six chromosomes, with any outliers involving missing or extra chromosomes – a teratoma with forty-five, forty-seven or
forty-eight chromosomes, not the twenty-three available in the egg. The missing or extra chromosomes do affect the development of the teratoma: having three copies of chromosome 13 has also been
implicated in the fused brain and ‘cyclops’ eye features that appeared on the Japanese homunculus. But the teratomas seem to gain or lose chromosomes fairly randomly; some have lost
chromosome 13; others have gained an extra copy of chromosome 21, which, in a fertilized embryo, sometimes causes Down syndrome. Not even the sex chromosomes are off-limits: though teratomas nearly
always have
the XX chromosome signature of a female, a few have been found to contain XXX (one extra X), XXXX (two extra Xs) or XO (a missing X). The one thing that seems to
be true of all teratomas, however, is that they never have a Y chromosome, which makes sense, since eggs should never carry this genetic material. Even without a Y, these kinds of tumours have been
known to grow prostate tissue, even more often than tumours of the male testis do.

The very fact that ovarian teratomas appear raises many intriguing questions. What makes an unfertilized egg start dividing? How does the teratoma end up with two or more sets of chromosomes,
when no other source – say, a father – has contributed to the teratoma’s creation? How is it that the teratoma can have two different versions of the same gene if it started life
as an egg, which would hold a copy of just one version? How does it grow prostate tissue or phallus-like organs when an egg has merely the X female sex chromosome at its disposal? And how does the
egg get around the requirement for other, non-genetic components, such as the centriole, which are usually the unrivalled domain of sperm?

Human eggs are formed early in life, when a woman is but an embryo, between three and eight months into development. After that, all the eggs can do is wait.

The waiting usually lasts many years – just over a decade or so, until sex hormones begin to exert their powerful effects. Hormones are chemicals, circulating in the blood stream, that act
on different target glands around the body. In women, the production of the sex hormones by the ovaries is stimulated by signals from the pituitary gland, a pea-sized structure at
the base of our brains. Once puberty hits, the ovaries produce oestradiol, progesterone, and testosterone in a choreographed manner, with levels of the hormones in the blood shifting
day by day in the dance from ovulation to menstruation or fertilization. Though it is a form of oestrogen, oestradiol is not a ‘female’ sex hormone as such; it is also produced in men
as a by-product of testosterone, as is progesterone. Oestradiol does, however, play a very important role in female fertility, triggering, for instance, the growth of a variety of reproductive
organs, including the vagina and the placenta. Progesterone, too, plays its part, including, it seems, in helping to keep the mother’s immune system from rejecting the embryo during
pregnancy. With puberty, eggs begin maturing at the rate of approximately one every month.

By around age fifty, give or take ten years, the majority of the eggs that were present at a woman’s birth have been released – either discarded during her monthly menstruation or
fertilized. Around this time, the ovaries stop acting on the signals from the pituitary, and oestradiol levels fall significantly – to around the same level as is present in men. Progesterone
levels also take a dive. This rapid loss of sex hormones in a woman’s blood stream is what causes the hallmark symptoms of menopause: hot flushes and sweating attacks; a rise in the risk of
heart disease and stroke; and osteoporosis, the ‘thinning’ of bones.

There are exceptions to the timing of the onset of menstruation and menopause, these critical moments at which the ovaries change their response to hormonal signals issuing from the brain. Just
as ovarian teratomas have been reported to be found in octogenarians, post-menopausal mothers crop up every so often. In 1987, a fifty-five-year-old British woman, Kathleen Campbell, gave birth to
a baby boy who was verified to be the product of natural conception – the oldest confirmed mother in the UK. Ten years later, a Welsh pensioner named Elizabeth
Buttle
claimed to have toppled that record by becoming pregnant naturally at age sixty. After Buttle sold her story to the
News of the World
tabloid, reportedly for £100,000, it came to light
that she may have actually been fifty-four, and that she may have been treated at a fertility clinic – neither of which, for privacy reasons, could be definitively confirmed. Mrs Buttle
referred to her son as her ‘little miracle’, and medical experts tended to agree. According to the
Independent
, doctors opined ‘that a natural birth to a woman of
fifty-four would be exceptional but to one of sixty it would be miraculous’. The legal wife of the baby’s father could not be swayed, however; she told the world that, for her at least,
miracle or not, the birth was not a cause for celebration.

Pre-teen pregnancies are even less a cause for celebration. But while women who have gone through their menopause must deliver a ‘miraculous’ egg, pre-pubescent girls simply need
some errant sex hormones to activate their more than plentiful supply, waiting for fertilization. And abnormal hormonal activity, including the early onset of puberty, is not unusual and, in fact,
is linked to hypothyroidism (when the thyroid gland does not make enough hormone, often caused by a diet lacking in iodine) and several other medical conditions.

Abnormal hormone levels have been known to trigger menstruation at an age when girls are still babies themselves. Take the case of the youngest mother in medical history, Lina Medina of
Antacancha, Peru, who had her first period at the age of eight months. At four years old, she had clearly developed breasts and pubic hair. A little more than a year later, in 1939, when she was
five years and seven months old, Lina gave birth to a healthy baby boy; she named him Gerardo after the obstetrician, Dr Géado Lozada, who had cared for her. Some in her native town likened
her to the Virgin Mary; others believed her child to be the son of the Incan sun god Inti. But, despite the fact that Lina
never revealed the identity of her son’s
father, and sad though it may be, Gerardo was not considered by her doctors to have been conceived without sin.

Similarly, in 1957, a nine-year-old girl was taken into the University of Arkansas Medical Center in Little Rock. Her mother had noticed that her stomach was getting rather big. Examining the
girl, the doctor felt a soft, movable lump, which he was convinced was a tumour. To confirm his suspicion, he performed an X-ray. But what he found was not just a lump; it turned out that the
girl’s periods had started at age eight, and her breasts had started developing the year before. ‘Subsequent talks with the patient reveal this not to be an immaculate
conception,’ the doctor said. Six days later, still in something of a state of shock, he noted in his records, ‘I cannot hear the foetal heart beat, but my “ovarian tumour”
has definitely kicked me!’

These extreme cases still involve not just hormones but fertilization, of course. Ovarian teratomas, however, are truly immaculate ‘conceptions’, coming from eggs
that at no stage have been fertilized. And yet, something happens in the body that overrides metaphase II arrest and sends the egg on the path of development, sometimes building remarkably
well-developed organs and features. Their origin is inextricably linked to parthenogenesis, but how exactly is the egg triggered to start dividing without first being fertilized? To this question,
certain mutant mice may hold the answer.

The structure of most cells in the body can be grossly divided into two areas: the nucleus and the cytoplasm. The nucleus can be thought of as the control centre of the cell. In the nucleus are
the chromosomes, which carry the vast majority of the cell’s
content of DNA, the all-important genetic instructions for the new being. The cytoplasm is a fluid matrix
that surrounds the nucleus and all the other
organelles
, or miniature vital ‘organs’ in a cell, providing the site for much of the cell’s chemical activity and manufacture
of protein-building blocks. So you can think of it as something like the factory floor to the nucleus’s administrative HQ.

During the creation of the cloned Dolly the sheep in 1998, through to the first cloned rhesus macaque monkey embryos in 2007, it was this nucleus-cytoplasm status quo that scientists considered
to be essential. In order to clone the sheep and the monkeys, researchers destroyed the DNA-containing nucleus of an unfertilized egg and replaced it with the nucleus of an adult cell. An electric
shock was used to activate the egg, instead of fertilization with sperm, and the resulting embryos – which were genetically identical to the adult cell but had no resemblance to the egg donor
– were implanted into the womb of a surrogate mother.

Paradoxically, research conducted in the 1960s had indicated that if you take the nucleus from one egg cell and place it into another, the nucleus that was introduced would adopt the behaviour
of the host cell rather than the host cell taking instructions from its new nucleus. The cytoplasm was dictating orders to the chromosomes in the nucleus, ‘telling’ the egg whether or
not to divide and mature – a case of the body controlling the brain, as it were, instead of the other way around.

In 1971, Yoshio Masui and Clement Markert of Yale University set up an experiment to work out what exactly in the cytoplasmic soup was pulling the nucleus’s strings. They found two
powerful ingredients. The first they called
maturation promoting factor
, or MPF, because it puts a cell on the road to mitosis or meiosis. The second they called
cytostatic factor
, or
CSF. It is CSF that prevents an egg from developing into an
embryo. CSF stalls meiosis in the egg through a delicate communication system of proteins. One of the proteins
certainly involved is Mos, which is made before the early egg embarks upon its first meiosis. If Mos is injected into a normally dividing embryo, all cell division stops. After successful
fertilization, Mos is destroyed in the cytoplasm, which allows cell division to get going. But Mos does not work on its own. Another protein, called Emi2, also helps to stop an egg from becoming an
embryo. All of this intricate chemical activity seems to exist for just one reason: to stop virgin births from occurring. Indeed,
c-mos
, the gene that encodes the Mos protein, is a
growth-controlling gene that has the ability, if it is mutated or otherwise unregulated, to cause a tumour to form.