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Authors: Aarathi Prasad

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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 the 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.

Some mammals, specifically marsupials such as the kangaroo and koala, have only a pseudo-placenta, which means that they must give birth at a very early stage of gestation. After that point, the
embryo – looking something like squirming larva – crawls from the womb and finds its way to the pouch covering the mother’s nipples, where it can suckle milk. The joey continues
to develop there, technically outside of the mother’s body, for many months. The pseudo-placenta in marsupials does not last long, nor is it very sophisticated.

The strange and complex approach to making babies in marsupial mammals reflects the strange and complex evolutionary history of the organ. In fact, the placenta has actually been
‘invented’ many times, in different families of animals. Fish have a version, in varying forms, and some sharks have a very advanced placenta, but no species have placentas quite like
those found among mammals. Mammalian placentas are extremely complex and structurally diverse, with up to six layers that connect the mother with the developing embryo. Genes have arisen to adapt
the mammalian placenta to a range of reproductive environments, to cater for situations as diverse as the twelve offspring expected after a mouse’s twenty-day
gestation, to the lone calf that results from an elephant’s two-year pregnancy. How the placenta evolved to meet these needs, and everything in between, remains a mystery.

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