Like a Virgin Read online

  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. A
nother 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.

  This connection between unregulated tumour growth and very regulated egg growth was tantalizing to scientists. So, in 1994, a team of researchers based at the University of Cambridge and New Zealand’s Ruakura Agricultural Centre created mice with a shorter than normal version of the c-mos gene. The smaller Mos protein produced from this mutant gene did not work and was unable to order around the cell in its usual way. In many of the mice with the defective Mos, eggs spontaneously divided – parthenogenesis. And one in three of these mutant mice developed ovarian teratomas.

  This seemed to be unmistakable evidence that the development of ovarian teratomas is related to mistakes in the c-mos gene. Except we know that the Mos protein does not play any significant role in the development of ovarian teratomas in humans. Human ovarian teratomas may come about because of mutations in any of several genes that, in their normal forms, make proteins that hold a cell’s development at bay, including Emi2.

  What else could make an unfertilized egg start dividing? It has long been known that fertilization by sperm triggers a surge of calcium into the egg. Indeed, in the lab, adding calcium to an egg is routinely used to start parthenogenesis. This offers scientists another candidate protein: calcineurin. Calcineurin is involved in immune system function, putting T cells into action, and mutant mice that cannot produce it exhibit behaviours similar to symptoms of schizophrenia. Calcineurin should be dependent on the presence of calcium to work, but a genetic mutation might allow it to work on its own.

  Finally, teratomas must get around the requirement for other, non-genetic components, such as the centriole, which are normally inherited from the father. In many species, including worms, snails, fish, and amphibians, the requirement for centrioles is the main preventative measure against virgin birth. In mammals, however, the process of moving the chromosomes around in the cell is a little more complicated. For instance, unfertilized mice eggs have centrioles, which organize the chromosomes inside. Human eggs also have centrioles, but they do not work, which is why human embryos inherit centrioles from the father. Maybe, once in a blue moon, those maternal centrioles have some say in what’s going on in the egg.

  In the Palais des Beaux-Arts in Lille, France, hangs a desolate but fantastical painting, The Concert in the Egg based on a drawing by the Dutch master Hieronymous Bosch. In it, you are confronted with an impossibly large egg, flanked by two withered trees – on one hangs a languid serpent, on the other, a wrinkled apple – as if the Garden of Eden had fallen into decrepitude. The egg is cracking open from the many characters it contains: bishops, nuns, simpletons, aristocrats, paupers, the elderly, the ill and infirm, even a monkey playing a pipe. Several of the characters hold a musical instrument: a flute, which was a common phallic symbol; the harp, representing the female sex organs; and the lute, associated with seduction. Fish, birds, monsters, and demons lurk around the egg, but the players seem oblivious. They continue their concert in complete absorption.

  In the sixteenth century, when the scene was painted, science had not even realized that there was such a thing as a human egg. And if there was the idea that women might, like hens, have eggs of their own, then it was not much more than wild speculation. But speculation set the wheels in motion, and by 1651, William Harvey, ‘Physician Extraordinary’ to King James I, was moving away from the realms of folklore and casual observation to form a medicine based on experimentation and precise measurement. Though best known for his seminal research into the workings of the circulatory system, Harvey also devoted considerable time to investigating reproduction, tinkering with chick embryos and, in perhaps his most audacious move, the royal herd of deer.

  Against the historical tide of spermists, Harvey claimed himself to be an ovist. Harvey believed that all life came from eggs: not just for birds, which was obvious, but for mammals too. He summed this up in his last work, Experiments Concerning the Generation of Animals. It was at odds with the generally accepted Aristotelian view that males contributed the lion’s share to the creation of new life through their sperm. After many years of research on the eggs of birds and deer, Harvey begged to differ. He was not able to provide a sound explanation for his ideas about reproduction, as he had done for the circulation of blood. Compared to the circulatory system, mammalian eggs were tiny and posed no small challenge to a scientist using seventeenth-century experimental tools. Only very cautiously, and after great persuasion, did Harvey publish his revolutionary book on sexual generation.

  The book begins with a frontispiece, reminiscent of The Concert in the Egg, in which Jove sits on a plinth while balancing an egg as large as an ostrich’s in his hands. The egg has split in two, and from it escapes an insect, a spider, a deer, a snake, a bird, a lizard, and various other creatures. Leaping out of the egg among them all is a cherubic human baby. Across the egg’s shell is scrawled Harvey’s hypothesis, ex ovo omnia – ‘out of the egg, all things’.

  Perhaps everything is contained in the egg, just waiting to be sprung into life. But although we now appreciate many of the egg’s complexities, there is a surprising amount that we still do not understand. What we do understand is that if the beautiful orchestration of genes, proteins, and hormones is disrupted, the egg can give rise to chaos. But although a rogue gene may be enough to kick an egg into forming an embryo, for humans, this is not enough to create a healthy child. However many human features there may be, the tertatomas born of eggs alone are still grotesque caricatures, with no hope of breathing life. There is a switch encoded in the genes of mammals that means that the healthy development of a bona fide virgin birth can happen only in truly exceptional circumstances.

  Quite on their own, our eggs can give rise to monsters and to mutants. But mostly what we observe are the success stories – the eggs that are fertilized and grow enough to be born into the world.

  5

  SECRETS OF THE WOMB

  A peace is of the nature of a conquest; For then both parties nobly are subdued, And neither party loser.

  William Shakespeare, Henry IV, Part 2, c. 1600

  In the early 1980s, a group of scientists were finding it very hard to convince themselves of something. They knew that a person needs two sets of chromosomes to come together in order to create the amount of DNA that a normal human, or for that matter, any mammal, has. So why couldn’t they make a healthy mouse in the laboratory that had two mothers or two fathers – the two necessary sets of chromosomes, though not from the usual two suspects? They had taken some early-stage embryos, removed the DNA that had come from the father, and replaced it with an equivalent set of maternal DNA from another egg. They also tried replacing the DNA from the mother with another set taken from sperm. None of these embryos survived.

  We humans could manage to concoct teratomas naturally with their monstrous lumps of skin, hair, and teeth, but that seemed to be the limit of what we could achieve without sex. Mammalian teratomas certainly jump developmental hurdles to develop incredibly sophisticated, if deformed, body parts. Why couldn’t a woman be more like a turkey? Why couldn’t we just clone ourselves? What was really standing in the way of a virgin birth?

  The answer may lie with a feature that no teratoma, in a woman or any other animal, has ever been found to grow: a placenta.

  On the simplest level, the placenta allows oxygen and carbon dioxide to be exchanged between two organisms: mother and foetus. It is also the medium through which vitamins, glucose, fatty acids, and other sources of nutrition are transmitted to the developing embryo. Yet, despite its essential function in reproduction, the placenta does not develop until adulthood; it is also the only organ to be discarded after it has served its purpose, only to be regenerated t
he next time it is needed.

  Perhaps because of this bizarre cycle of creation and destruction, cultures throughout the world have developed practices, rituals, and myths around the placenta, to account both for its importance and its impermanence. Many animals – including some humans – eat it. Indeed, there are numerous recipes online for anyone who wants to savour one, including such delights as roast placenta (with bay leaves, a tomato sauce, and peppers), placenta cocktail (chilled, with vegetable juice), and placenta lasagne, or bolognaise. You can even dehydrate and use it much like a chorizo.

  In some cultures, the placenta is buried with great ceremony after the birth of a child. In Hawaii, this tradition was briefly made illegal, until a law came into force in 2006 that guarantees a woman’s right to take her placenta home from the hospital so that she can perform the rite. In Malaysia, the placenta is considered a baby’s sibling; in Mexico, its friend, el compañero – a good description since, for humans, the placenta truly is indispensable. Without it, humans could not give birth to live babies; it supplies all the things that a foetus in the womb cannot get for itself.

  The appearance of mammals, as well as snakes, birds, and lizards from a common ancestor back in the Jurassic period – about a hundred and fifty million to two hundred million years ago – was dependent on the evolution of this remarkable organ. From elephants to elephant shrews, and from dolphins to flying lemurs, the overwhelming majority of the 4600-odd species of mammals alive today develop a true placenta, allowing offspring to emerge from a mother’s body with well-developed organs after an extended period germinating in the womb.