Of course, sugar isn’t the only resource over which the mother and the foetus are fighting. By the sixth month of pregnancy, the mother’s body has produced an extra 1.4 litres (2.5 pints) of blood to support the foetus’s growing needs for oxygen and other nutrients. Pumping this extra blood around the body requires some changes to the woman’s circulatory system. Levels of the hormone progesterone increase, to relax and expand the blood vessels in an effort to accommodate the extra flow. In the best-case scenario, this extra rush of blood makes a woman feel unusually hot and involves a drop in blood pressure, which might cause dizziness, or the occasional faint. But when there is a poor exchange of blood between the mother and the foetus, the body has to find ways to push this extra blood in and out of the placenta, and brute force is the answer. Blood pressure rises in compensation. Approximately fifteen million pregnant women experience high blood pressure around the world each year. And one of the reasons pregnant women are constantly having their blood pressure measured is to assess the chances of a medical condition called pre-eclampsia.
Eclampsia in humans was recorded in early Egyptian, Chinese, and Indian medical texts dating as far back as four thousand years ago – not surprising, since the condition involves spectacular, life-threatening complications that would be evident without any knowledge of the interior anatomy and genetic developments involved in pregnancy. If pre-eclampsia isn’t spotted and prevented, sudden convulsions can develop during labour. When full eclampsia sets in, the mother’s mouth twitches and her body contracts, then becomes completely rigid; violent muscular spasms break out and the woman foams at the mouth. So alarming is this complication that it probably prompted the first Caesarean sections to be conducted about two thousand years ago. Unfortunately, eclampsia remains a serious, potentially fatal condition, and can harm a woman’s kidneys, liver, and blood vessels.
These terrible complications, however, do not affect all animals with placentas. In fact, they are only known to happen in three species alive today: patas monkeys, lowland gorillas, and us. What distinguishes these three primates from other mammals is the extent to which the placenta penetrates the mother’s blood supply. If the placenta does not invade deep enough, the mother’s heart has to work harder, increasing the pressure of the blood in order to keep the foetus alive.
The link between pre-eclampsia and high blood pressure has been acknowledged since 1896, when the inflatable arm-band for measuring blood pressure was invented, but doctors still do not know exactly why, in some women, the placenta stops receiving blood as it should. The only risk factor that is universally accepted is being pregnant for the first time. Why should that be?
Our immune systems evolved to protect us from a staggering variety of parasites – anything that is in our bodies that shouldn’t be. Once an outsider is recognized, the body’s aim is to get rid of it. But we have seen that evolution has worked around this line of defence in many ways, for the simple reason that if a species is reproducing via sex, it benefits the mother’s genes to become pregnant. Yet, it isn’t easy for foreign sperm to get to an egg. Out of the three hundred million sperm that might be released into a woman’s vagina, only one, if any, will normally succeed in fertilizing an egg. All the barriers are in place to prevent it: to prevent infection, the woman’s vagina has an acidic pH that is also a killer for sperm; to stop microbes from invading, the cervix is filled with compact mucus, which also makes it incredibly difficult for sperm to make it to the womb; and then, the womb is armed with the soldiers of the immune system, white blood cells, which will physically engulf and destroy unwanted invaders, including most sperm. In pre-eclampsia, it may be that the woman’s immune system has put up yet another line of defence and refuses to accept the incursion of the placenta’s foreign DNA.
Pre-eclampsia occurs mostly in first-time pregnancies, but not all first-time pregnancies are the same. If a couple has had unprotected sex for less than four months before conception, the rate of pre-eclampsia is approximately four out of five. This decreases to one in four among those couples who have been having unprotected sex for five to eight months, and further to one in twenty among those who have been doing so for more than twelve months. Even a woman who has already conceived several children runs a heightened first-time-pregnancy risk when she takes a new male partner who isn’t the father of her earlier children. Put simply, it may be that being exposed to a particular partner’s sperm ‘acclimatizes’ a woman’s immune system to his genes, breaking down the defences against foreign intruders and improving the negotiations that take place between the womb and the child. Becoming tolerant of a partner’s sperm appears to protect the mother and the embryo, once it implants in the woman’s womb.
So while humans may not ourselves be strictly monogamous, evolution has built women to have more successful pregnancies with long-term sexual partners.
During pregnancy, the mother, too, has an active role in protecting the foetus from her immune system’s attackers: substantial numbers of a woman’s immune cells cross through the placenta and settle in the developing lymph nodes of the foetus, disguising the baby’s immune system from her own. In a way, the body is tricked into seeing the foetus as a ‘temporary self’. These cells also serve to suppress the foetus’s immune system, which could be set against the mother’s blood.
These maternal immune cells have an incredibly long-lasting influence on the foetus, even long after the baby is born. As they cross from the mother to the child, the cells ‘teach’ the foetus how to balance the need for self-defence against the need for tolerance to the surrounding environment. This is a tricky balancing act. If the foetus is taught to be too tolerant, the newborn baby may be left unprotected from a common but potentially lethal infection. If, on the other hand, the foetus’s self-defence mechanisms become too keen, a child may be overly sensitive to certain foods and environments; worse, the body might start attacking itself – a condition called autoimmunity. Indeed, until at least early adulthood, a mother’s immune cells influence how her child’s body regulates its own defences and how tolerant, or susceptible, it will be to allergies and infection.
It used to be thought that a baby in the womb somehow made itself completely invisible to the mother’s immune system, but this isn’t strictly true. What happens, instead, is that the immune systems become interlocked. This means that diseases which are not normally transmissible between two adults can pass from mother to child. Diseases such as cancer.
In 2007, a twenty-eight-year-old Japanese woman gave birth to a girl. The pregnancy was uneventful, and the baby seemed perfectly healthy on delivery. When the baby was about one month old, however, the mother had to be rushed back into hospital: she was bleeding uncontrollably from her vagina. She died not long after being admitted. Although she had not known it, the mother had leukaemia, a cancer of the bone marrow and white blood cells, which is known to be a possible underlying cause of haemorrhaging after giving birth. Eleven months later, doctors found a huge tumour trapped in the baby’s cheek.
Cancer cells tend to be pretty well skilled at making themselves invisible to the immune system. Mostly, this is because they are actually our own cells, not foreign invaders, and the disease comes from mutations that make the cells incapable of regulating their own growth. They divide and spread and expand in ways that would usually mark them for self-destruction. But they grow on. That doesn’t explain, however, why the mother’s cancer cells would not be attacked by the baby’s immune system.
When the doctors studied the cancer cells in the Japanese baby and samples taken from her deceased mother, they found that the cancer cells were missing a large chunk of DNA from chromosome 6. It is along this stretch of chromosome that the DNA normally produces the markers on to which our immune cells latch. In this case, the cancer cells passed from mother to child because the immune cells were not able to attack, and there was nothing the baby – no matter how vigilant her immune system might be – could do about it.
Inside the water
y world of the womb, the growing baby receives many cues that affect its health. The body is primed in the womb for the environment in which the mother already lives. That, in turn, should increase the child’s own chances of growing to adulthood and reproducing successfully.
For example, if a mother eats too much or goes hungry, the foetus will adjust its nutritional needs in both the short and long term, preparing itself for a world in which it will either have easy access to food or need to be ready to go without. Among the most well-publicized studies of nutrition in the womb are studies of rodents that have had their diets restricted. In particular, scientists have been interested to find out how a mother’s calorie intake affects her fertility and the survival of her young. You might guess that a hungry mother rat would have fewer nutrients to share with its foetuses, and that less food would mean less offspring. This isn’t the case. When female rats were fed a calorie-restricted diet, the mothers enjoyed a longer span of fertility, giving birth to pups at more advanced ages. And when these dieting rats gave birth, the survival rates of their pups were dramatically better than for the offspring of rats that were allowed to eat to their heart’s content. For mother rats whose calorie intake was moderately restricted, over seventy-three percent of pups survived, whereas only twenty-two percent of pups survived that were born to mothers with an unrestricted diet.
Like the propensity to be allergic, however, humans are also programmed in ways that can make us oversensitive to certain chemicals, putting us at risk for related diseases. Coronary heart disease may also have its origins in the womb. Pregnant women who have impulsive, uncontrollable outbursts of temper (more incidents of slamming doors; loud, angry shouting; binge eating or drinking; smashing dishes; etc.) secrete higher levels of stress hormones, such as cortisol, which can cross through the placenta and reach the baby in the womb. Once there, the hormones change the way in which the hypothalamic-pituitary-adrenal axis, or HPA, and the autonomic nervous system work, and both the HPA and this part of the nervous system appear to be important for programming disease into the foetus. Individuals who were overexposed to stress hormones in the womb exhibit long-term, stress-related behaviour as adults. These hormones also affect foetal heart development and may increase the risk for developing cardiovascular disease later in life. Being overweight is associated with the release of inflammatory factors in the body, and these factors can also affect the development of the lungs and the immune system in a foetus. So if a mother is overweight, her child may also have a higher risk of developing allergies and asthma.
Obesity, in particular, may be decided in the womb – long before a child gets around to putting anything into his or her mouth. If a mother gains excessive weight or has diabetes while she is pregnant, the foetus will adapt to an environment where there is an excess of sugar around. As a teenager, her child is more likely to have a high body mass index, or BMI, even if the child does not eat fatty foods. Mice or rats that are put on a high-fat and high-sugar diet that makes them obese have pups that grow up to have increased body fat and abnormally large appetites. In fact, even when these pups are kept on a healthy diet, their appetites mean they are far more likely to become obese on standard meals. They also have an abnormally high level in the blood of the protein leptin, which has a starring role in the way food is consumed and then metabolized into energy by the body. Other experiments on animals indicate that if a mother’s nutrition becomes imbalanced during pregnancy and breastfeeding, this permanently changes how – at the level of the brain – her offspring consume food as adults. The mother’s patterns of consumption actually alter the developing hypothalamus, the almond-sized part of the brain that controls basic biological functions such as hunger, thirst, fatigue, and temperature. The hypothalamus produces the hormones that control when we feel hungry and desire food, as well as those that control aggression and sexual behaviour.
Bizarrely, because of how imprinting works, a father also sways his child’s life after birth, through the timed influence of his genes. Some of a father’s genes, in fact, only become expressed after a baby has been weaned, and they can have a significant effect at much later stages of life. For instance, the father’s genes have a say in whether or not a child develops disorders related to food, possibly including obesity. Here, once again, we see the battle between the father’s DNA and the mother’s body.
This is because those eighty genes that are subject to imprinting have an important say in the development of our brains. Those genes that are silenced when inherited from the mother but expressed when inherited from the father inhibit our overall brain size; they contribute to the development of the hypothalamus – the impulse centre that makes us crave food. In contrast, the imprinted genes that are expressed when inherited from the mother contribute to the cortex, the so-called grey matter of higher mental functions; the striatum, which is involved in decision-making and risk-taking; and the hippocampus, the brain’s memory centre. Recent molecular analysis has shown that among people who carry defects or mutations in genes that are supposed to be imprinted, there is a surprisingly large incidence of cognitive, behavioural, neurological, and psychiatric conditions. These include autism, bipolar affective disorder, epilepsy, schizophrenia, and Tourette’s syndrome.
This sex divide in the role of imprinted genes on the brain is curious, because what happens in the hypothalamus is also believed to influence maternal behaviour. Studies in mice have shown that mothers will neglect their offspring if the PEG1 gene (paternally expressed gene 1) is removed from their fathers so that they are not able to inherit it. A related gene, called PEG3, increases maternal care, too, and also regulates male sexual behaviour – meaning it ensures its own preservation. If a male mouse does not have the PEG3 gene, then, no matter how much sexual experience it gains, it is unable to improve its reproductive effectiveness; for example, no amount of experience will make the mouse better able to recognize the odours that female mice secrete when they are ready to mate. It seems that a father can even directly influence how his daughter will behave towards her own children, through imprinted genes alone.
For mice and men (and women), evolution has pitched mother against father, father against mother, mother against child, and child against mother – our genetic sources and our genetic creations are all battling for control. The outcome of these long-ago skirmishes is a treaty written in DNA: neither a mother nor a father may use all the genes at their disposal, but both will have a genetic and a chemical voice that will continue whispering into the brains of their children – all the way into adulthood. Neither sex can do without the other. At least, that is, while we are still constrained by the body.
But what comes next? Will those restrictions still hold when eggs and sperm and foetuses and wombs are no longer tied to biological packages of human anatomy? Because, if the past centuries of discovery show anything, it is that once science stumbles upon an obstacle, the next step is to tear that obstacle to bits, find out how it works, and then see if we might get rid of it altogether.
PART II
A NEW WAY OF MAKING BABIES
All our science is just a cookery book, with an orthodox theory of cooking that nobody’s allowed to question, and a list of recipes that mustn’t be added to except by special permission from the head cook.
Aldous Huxley
6
OUT OF THE TEST TUBE
If every physical and chemical invention is a blasphemy, every biological invention is a perversion... And all this of course applies much more strongly to the sexual act.
J. B. S. Haldane, Daedalus, 1923
On 27 July 1978, the front page of the London Evening News carried a nearly life-sized photograph of a beautiful infant, a mere eighteen hours old. She was wide-eyed and swaddled all in white, a perfect specimen of just-born humanity, and she was pictured below the headline – superbabe – that announced her birth.
Louise Joy Brown was no ordinary newborn, but ‘the world’s first test-tube arrival’, a child widely ce
lebrated as a miracle of science. As her middle name testified, Louise was an even greater miracle to her infertile mother, thirty-year-old Lesley Brown, whose grossly distorted and persistently blocked Fallopian tubes had made it impossible for her to become pregnant over the course of nine arduous and depressing years. Louise was the first child to be born through in vitro fertilization, or IVF.
Medical science had been wrestling with infertility for quite some time. But because the subject has been (until very recently) shrouded in secrecy, it is almost impossible to say with any accuracy when artificial insemination in humans was first attempted by doctors. ‘Historically, artificial insemination is one of those rare medical entities which cannot be traced back to Hippocrates,’ wrote one American obstetrician back in 1943. Yet, we can trace the practice to at least the middle of the fifteenth century, when a French doctor called de Villeneuve performed artificial insemination for King Henry IV of Castile and his second wife, Joan of Portugal. The king was rather unkindly nicknamed ‘The Impotent’ – and although local prostitutes confessed to a priest that their monarch was perfectly sexually capable, close examination confirmed that he could not, indeed, get an erection. Artificial insemination, however, was not successful. De Villeneuve could not have known that King Henry was probably living with a pituitary tumour or a condition known as hypogonadism, either of which would have rendered him completely sterile. So whatever ejaculate he could supply to his doctor contained little or no sperm. Even if de Villeneuve had managed to introduce the royal semen into Joan’s womb, pregnancy would have been near impossible. Fortuitously, his wife took matters into her own hands and bore three children by natural donor insemination – that is to say, the children were, reportedly, fathered in amorous liaisons with the Duke of Albuquerque and with the nephew of a Church bishop.
Like a Virgin Page 13
