Like a Virgin Read online

  Mission impossible? It should be. Yet, some animal eggs regularly manage to achieve virgin births – not just tiny insects, but large vertebrates, including fish, birds, and reptiles. And, in fact, human eggs can work on their own too.

  Most animals have eggs with a lot in common. Of the billion or so cells in our bodies, the egg is the largest cell that animals have. Among most amphibians and fish, an egg is about as big as the full stop at the end of this sentence. If you divided that full stop into one hundred pieces, most other cells in their bodies would be about the size of just one of those bits. Human eggs, by comparison, are the size of ten pieces. Reptiles and birds, of course, have immense eggs – each egg in the cardboard carton you bring home from the supermarket to scramble up for your breakfast is essentially a single egg cell.

  The mammalian egg is the site of a number of quite extraordinary biological processes, not least of which is the way the egg itself is produced. The first person to figure out that there was something unusual about eggs was Edouard Van Beneden, in 1883. At the time, Van Beneden was studying how the cells in Ascaris megalocephala, a worm parasite of horses, were made. By throwing live female worms into containers filled with diluted alcohol and leaving them there to ‘stew’ for several months, he was able to dissolve the worms’ cells enough to reveal their components. (This method of damaging cells is still used in labs to isolate DNA and RNA; it’s also the reason why alcohol wipes are effective at killing bacteria.) Van Beneden observed that the worms had four chromosomes in almost all of their cells. In their eggs, however, there were just two chromosomes. To Van Beneden, this made no sense: the eggs were made from cells with four chromosomes, so two chromosomes had seemingly disappeared. He then noticed that the mother’s and the father’s chromosomes came together in the fertilized egg, thus producing baby worm cells with four chromosomes. The contradiction puzzled him, and he did not publish any further work on the subject.

  A year later, Van Beneden’s work came to the attention of the German biologist August Weismann. Alas, the esteemed professor was suffering from eye trouble. After many years of conducting his groundbreaking scientific experiments in chemistry, biology, and medicine, he could no longer look down the microscope for himself, and he was forced to turn his attention to theoretical questions. Still, he was not ready to give up experimentation altogether. Weismann asked his janitor to carry out the logistics of his experiments and assigned his students to do the microscopic analysis. His wife, Marie, would read scientific papers aloud to him, so that he could keep up with the latest ideas. Among the papers Marie recited was Van Beneden’s work on chromosomes in worm eggs. As Weismann listened to Van Beneden’s extensive observations, and Marie’s descriptions of the paper’s drawings, he came up with a theory: a very special division happened exclusively in the sex – or germ – cells, that is, in eggs and sperm.

  For every cell in your body that isn’t an egg (for a woman) or a sperm (for a man), making a new cell is a simple case of copying the chromosomes, separating the copies into two lots, and then distributing the original set and its copy equally into two new cells. This process is called mitosis. Think of it as making a photocopy of some pages: you separate the original pages from the copied pages, keep the originals for yourself, and give the photostats to a colleague.

  Weismann realized that a different division must also occur in order to make a sex cell. Whatever number of chromosomes there were in the original cells, these would need to be halved, resulting in that sex cell with only one set of chromosomes. He had discovered meiosis, a process that only ever happens in eggs and sperm, and the thing that makes sex exciting, in evolutionary terms; meiosis ups the ante in the grand gamble of reproduction. The word ‘meiosis’ is derived from the Greek for ‘diminution’, because, as Van Beneden and Weismann observed through their microscopes, duplicated DNA from a sex cell that is dividing is diminished by half in the new cells that are produced. (The devices available to them were not quite sophisticated enough to demonstrate that, in reality, meiosis achieves far more than that.)

  Whereas most cells of our body contain one maternal chromosome and one paternal chromosome, each copied as precisely as possible, an egg or sperm must contain only one chromosome strand, and the copies of the chromosomes that end up in the egg or sperm are not simple duplicates of the strand in other cells. The process of meiosis physically shuffles and exchanges information between the two chromosome strands. To do this, the double helix of the chromosomes breaks, and the broken ends physically move across each other, swapping genes before the double helix re-forms. This is a much greater challenge than the usual process of cell division, because genes must be matched, sorted, scrambled, redistributed, and realigned. From this, a unique combination of genes is born. It is different to the gene combination found in either parent, different to the one inherited in every other body cell, and peculiar to the offspring that may be created when this sexual cell fuses with a mate’s. It is for this reason that no two children born to the same parents, unless they are identical twins developed from a lone fertilized egg, are genetically the same.

  At the end of this complicated process, it is not just how the chromosomes are divided up that makes the egg especially unique. Inside the egg, there is also a cellular ‘soup’, which separates into two grossly unequal parts. The disproportionately smaller of the two parts helps to reduce the number of chromosomes until only one set of the two is left. Ultimately, that smaller part degenerates while the larger one sticks around to become the egg, ready and waiting to be fertilized.

  This rudimentary, immature egg will then undergo a second meiosis, just as complicated as the first. Another unequal division of a cellular soup produces a tiny cell and a fully mature egg. Like the last one, this tiny cell is usually destroyed, but not always. In the fruit fly Drosophila melanogaster, this tiny cell sometimes ‘fertilizes’ the larger, mature egg to create virgin-born fly offspring, essentially using a part of the egg to stand in for sperm. In humans (and almost all vertebrate animals), right in the middle of this second meiosis, the egg stops dividing and enters a biological holding period, known as prophase I, in which it can remain for an extraordinarily long time. In frogs, this phase can last several years; in humans, several decades.

  When a girl enters puberty and starts ovulating, the egg will resume its monthly meiosis. But there is another catch: the egg will be blocked from maturing further or transforming into an embryo until and unless some sperm show up. This block on development is dramatically named metaphase II arrest. Eggs need to be activated to start their dividing, and activation usually happens with fertilization – the fusion of sperm and egg. At least, that is, when things are proceeding normally.

  Moment by moment in the course of your life, cells in your body are dying off. Before they do so, they divide and give rise to ‘replacement’ cells just like themselves – a skin cell divides into two new skin cells; a liver cell into two liver cells – which is how the body doesn’t dissolve into non-existence. But when eggs divide, they can give rise to every cell type that exists in the adult, creating, over a series of cell divisions, a complete new individual – sometimes, in a matter of days. No other cell can match this feat.

  A beautifully orchestrated concert ensues in an animal egg after fertilization occurs. Like a pool bursting with the elegant and energetic motions of a team of synchronized swimmers, molecules interact and cells cluster and move around to the very spot where they will be called upon to shape a new creature in early, miniature formation. Soon (in humans, about fifteen days later), the early embryo organizes itself from a simple ball of cells into an organism made up into what are called germ layers: the ectoderm (the ‘outer skin’ in Greek), the mesoderm (the ‘middle skin’), and the endoderm (the ‘inner skin’) in all vertebrates. These skins are literally the layers that build us, and are responsible for forming all the structures and organs present in a fully developed animal body. It is now that a recognizable body plan begins to be laid ou
t.

  The endoderm, the innermost of the three layers, forms a simple tube, which will eventually become the digestive tract, connecting the mouth to the anus. The tube will differentiate into parts as diverse as the pharynx, which helps us to speak; the oesophagus, the ‘entrance for eating’; the trachea, or windpipe; the salivary glands; the liver; the pancreas and certain glands of the pancreatic system; and even the lungs – the respiratory and digestive systems being intricately connected. The mesoderm gives rise to the muscular and fibrous tissues – the muscles, including the heart; connective tissues, cartilage, bones, bone marrow, blood, and the epithelia that line the blood vessels; the lymphatic vessels and lymphoid tissues; the reproductive organs and the urinary system; and the notochord, a column of tissue that bisects the embryo into left and right sides, and which later develops into the vertebral column. The ectoderm becomes the brain and spinal cord, via a process in which a part of the layer rolls up into a tube and pinches itself off from the rest. As it pinches off, some ectodermal cells escape into the mesoderm, where they form part of the nervous system as well as the pigment cells of the skin. The rest of the ectoderm envelops the embryo with what will become the epidermis – the outer layer of our skin – complete with sweat glands, hair, nails, and teeth.

  An egg trying to make all this stuff on its own is up against a number of natural obstacles. For one, an egg has only one set of DNA, but its offspring requires at least two, to get that right number of chromosomes. Second, to start the process of separating, copying, and dividing up its chromosomes, the egg needs some centrioles – barrel-shaped cellular structures, provided by sperm, that help to move the chromosomes around during cell division. Third, at some point along the way to becoming an embryo, the egg will face the roadblock of metaphase II arrest. And for mammalian and marsupial eggs, there is a fourth challenge: evolution has locked some genes so they just won’t work for creating offspring. Still, some human eggs have gone solo – or perhaps it’s more precise to say that they have gone rogue.

  The main evidence for the human egg’s capacity to develop on its own comes from teratomas – shocking, grotesque cell masses that appear to be an amalgamation of unfinished or discarded body parts. Mature teratomas are a rare form of benign tumour made up of varying combinations of ectoderm, mesoderm, and endoderm tissues. They have been documented in guinea pigs, dogs, cats, horses, marmosets, rhesus monkeys, baboons, and humans. Some teratomas are smooth, shiny balls of skin; others, a bloody fur ball of hair; yet others a lump of raw flesh spiked with perfectly formed teeth. Often, under their skins, they also contain organ systems and major body parts. It may not come as a surprise, then, that teratoma comes from the Greek for ‘monstrous tumour’.

  Ovarian teratomas, which grow from egg cells, have been identified in girls as young as two and women as old as eighty-eight, but they mostly tend to develop in women in their twenties or thirties, or ‘late’ reproductive age. Studies of twins indicate that the propensity to develop ovarian teratomas may be inherited. These teratomas are quite distinct from the more highly developed growths known as fetus-in-fetu – malformed, parasitic twins that grow inside a living person’s body. Fetus-in-fetu are the product of normal conception, while ovarian teratomas come from eggs that have never had a whiff of a sperm cell. Essentially, they are unfertilized eggs that didn’t or couldn’t respond to the signals to stop and restart developing – the usual holding periods involved in readying an egg for reproduction.

  The vast majority of ovarian teratomas recorded in humans have gone so far as to develop such features as skin, hair, and teeth. In twenty-four known cases, ovarian teratomas have contained a homunculus – a mini-human, or partial, foetus-like structure, something straight out of Paracelsus. The Latin term homunculus roughly translates as ‘a structure resembling a miniature human body’ and today is used by doctors to describe a growth of tissue that has the features of a human being but which was not produced by pregnancy.

  In 2002, a twenty-three-year-old woman was admitted to the Korean University hospital with a huge lump in her pelvic area. It was soft to the touch, and it moved around when prodded. The patient had never been pregnant and had regular periods; her womb and her Fallopian tubes were normal. Doctors performed an ultrasound and found that, in fact, the woman had two lumps, one in each ovary. The masses were removed and dissected. Both had smooth, glistening surfaces and measured about fifteen centimetres in diameter. One of the lumps contained another, smaller cyst, filled with hair intermixed with a greasy yellow substance and some fluid. The other lump was more surprising. Encased in a tortuous network of blood vessels, the doctors uncovered another, smaller growth. There were no muscles, ligaments, or organs inside the homunculus, but from the outside it looked eerily like a tiny, dismembered baby, lying face down, with only a hirsute head and part of its right arm formed. The head was partially split open, and from it spilled a herniated brain. X-rays revealed an imperfect but impressively well-crafted skull, shaped somewhat like a cross between a Spartan and a Samurai helmet. The skull bones included easily recognizable structures, including a cranium and a jawbone.

  The following year, in 2003, Japanese doctors operating on a twenty-five-year-old virgin identified the most fully formed teratoma found to date. Once again the outer layer of the tumour was filled with a mixture of hair and fat. Cutting through this mess of cells, the woman’s doctors found a solid, hard lump. When the lump was cleaned up, the doctors could see that it was a small, ‘doll-like’ body, mostly complete. Like any normal foetus, the body was covered with fine, downy hair, but the homunculus was unmistakably deformed. It appeared to have spina bifida, a condition in which the ectoderm doesn’t quite finish rolling up into the spinal column (the name is Latin for ‘split spine’). Its head exhibited malformations normally seen in babies with holoprosencephalia, which occurs when the forebrain of the embryo fails to divide fully into two normal hemispheres. In the centre of the forehead was a single soft, spherical, fluid-filled ‘eye’ cloaked by thick, long eyelashes – a disorder named cyclopia, for the one-eyed Cyclops of Greek mythology. This strange foetus had one ear, all its limbs, a brain, a spinal nerve, intestines, bones, and blood vessels – even a jaw, already ruptured by several teeth, emerging from beneath the skin. Paradoxically, it also had what looked like a phallus, positioned neatly between its legs.

  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 ovar
ian 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?