Fat, Fate, and Disease : Why we are losing the war against obesity and chronic disease (17 page)

Even the number of cells which store white fat (technically called adipocytes) in our bodies is set during early life. Many fat cells are
made before we are born and their number is essentially fixed by the time that we are adolescents. Of course they can expand or shrink, depending on how much fat is contained within them, but their number is relatively constant.

The number of brain cells, the number of muscle cells, the number of cells in the pancreas that make insulin … they all follow a very similar pattern. Recent research shows that there are stem cells in fat and muscle and in the brain that may allow some new cells to be made under particular conditions but, relative to the total number of cells we need, these are very small effects. Indeed one of the biggest challenges in medical research is to see whether we can find a way to activate these stem cells or to create more of them to help repair organs when they become damaged or aged. Stem cell injections are another possibility and we already use such treatment in cancer whereby blood stem cells from the bone marrow are transplanted into people whose own stem cells have been destroyed by chemotherapy and radiotherapy. There is also experimental work to inject stems cells into damaged hearts to try to repair the dead muscle following a heart attack—it looks promising, but it is not routine care as yet. These techniques offer hope that we may be able to assist the function of bodies at times when their destiny, as set in early life, is beginning to look bleak.

The hardest problems to deal with in life are those that we can’t see. If you are out for a country walk and you suddenly feel a sharp pain in your arm, you may look down and see a wasp on your arm. This is annoying, but at least you have a clear idea of the nature of the problem. You can decide how to deal with it over the next few days. Does it need an anti-inflammatory cream? Is it getting more swollen and painful? Perhaps you are allergic to wasp stings or maybe the site of the sting is becoming infected. You monitor the situation. Pain in the arm which is not associated with any obvious injury is more
worrying. If it persists you will need to seek medical help and this may lead to a long series of investigations. It may be associated with a heart problem; it may be the early sign of a neurological condition; it might be due to a bone tumour … or it may just be a sprain, or be inexplicable, and will disappear in a week or so.

So it is with life before birth. It is often said that being born is the second most dangerous time in our lives. Certainly the statistics bear this out because, in the absence of modern medical care, the risk of dying from lack of oxygen or other problems around the time of birth is over 10 per cent. Such deaths can still occur even with the most advanced medical care, but their prevention has been the focus of modern obstetrics and paediatrics, and for those of us in the West it has been a remarkable success story. Fewer than five babies in every 1,000 live births will die in a developed country, and most of those have major medical problems or are born extremely prematurely. Much of that success has come about because we have developed ways of observing the fetus, assessing its health, and then keeping an eye on how it is coping with the dramatic events of being born. And so we can deal with the complications that may occur in the birth process—if necessary, we can perform an emergency Caesarean section, or resuscitate the baby if it is not breathing adequately after birth. One of the most dramatic advances in all of medicine has been the ability to keep premature babies alive. Forty years ago it was rare for any baby born at less that 34 weeks of gestation to survive; now it is routine for babies as young as 26 weeks to survive, and some do so from as early as 22 weeks’ gestation (although many of these cases will have less than ideal outcomes).

We can evaluate the health of the fetus remotely using ultrasound or by measuring some critical aspects of fetal life, such as heart rate, via electrodes placed on the mother’s abdomen or simply by listening with a stethoscope. We can measure fetal movements. We can use hormone measurements in the mother’s blood to ascertain the health of the placenta. If we need to, we can even use a fine needle
to draw amniotic fluid from the sac that surrounds the fetus or even fetal blood from the umbilical cord to measure the baby’s nutrient, growth factor, and hormone levels. All these methods give us a very good idea of how well the fetus is coping, in much the same way as a paramedic might take measurements of a person at the site of an accident. In the absence of such monitoring, problems can creep up unnoticed and become life-threatening in a very short period of time.

But these are the successes of Western medicine. In much of the world this is not routine practice—sadly, about half a million women die in childbirth or from conditions related to pregnancy every year, and throughout the world a baby under a year old dies from such problems about every 4 seconds; about eight million per year. Less than half the mothers and babies in the world are attended at birth by a trained midwife, and many more than half of all babies at birth do not have the most basic of health assessments made—they are not even weighed.

Birth is the culmination of many months of growth and development within the womb. There is no shortage of challenges or problems which can occur during that time. The fetus appears able to cope with many of these unaided, and in fact it is so good at doing this that we may never know that it has faced any problems at all. But the more we look, the more we find that there are subtle echoes of these experiences that have a cost in terms of later health.

There has been a dramatic change in our understanding of fetal development over about the past 50 years and this has led to a major re-evaluation of the answer to that most fundamental of questions—what makes us what we are? The study of development has emerged as perhaps the most exciting part of modern biology—be it in understanding how one fertilized egg can become the complex being that we are, or the subtleties of how seemingly small differences in developmental experiences can have lifelong effects in making us all different.

For most of human history our development before birth remained a complete mystery. The ancient anatomists, such as Galen, dissected the bodies of pregnant women—many of these were condemned criminals and most, but probably not all, were dead at the time—and were able to describe some of the key features of the anatomy of the developing fetus, its placenta, and the environment in which it lived. But we can only learn so much from anatomy. In the absence of anaesthesia or sterile surgical techniques, it was not possible to study developmental function to follow how the fetus grew along its own characteristic path and the adjustments which it made to its structure and function along the way. Knowledge of such adjustments had to wait until the invention of ultrasound and techniques for monitoring fetal growth and development in pregnant animals.

The new knowledge gained by such advances led us to radically revise our ideas about fetal life. Because it was known that the fetus could not survive outside the womb, at least until very late in gestation, it was believed that it must be entirely dependent on its mother, not only for survival but also for the regulation and control of all aspects of its growth and development.

We can see why this idea was so widely believed. All pregnant women detect the movements of their fetuses and can describe the many ways in which the baby seems to respond to what is happening to them—for example, a sudden loud noise such as a passing train may startle the fetus just as much as the mother. The fetus is particularly active after the mother has had a meal, as if it seems to have taken on board more fuel and is now doing some aerobics. In folklore there were many explanations of what are called ‘maternal impressions’. For example, if a woman were frightened by a bull in pregnancy, her child was expected to manifest some bovine characteristics. There is absolutely no truth in such stories, but we can see how they might have arisen in an attempt to understand how
problems—for example, Siamese twins, or babies born with a cleft palate or a strawberry birth mark—had occurred during the secret life in the womb. This rudimentary folk knowledge gave us very little insight into the way in which the fetus is able to control its own life and influence its destiny.

But fetal life is in fact very different from this. We have now gained enormous insights into all sorts of subtle ‘decisions’ which control our lives within the womb and influence our destiny after we are born. They are highly sensitive and effective and start very early in gestation, actually when we are still a tiny embryo. The fetus does not merely sit around or doze peacefully during the long months before birth, as if it were waiting for its real life to begin—far from it. It is continuously detecting signals about the world outside, transmitted through the medium of its mother and the placenta, and adjusting the course of its development accordingly. It measures the level of the nutrients which are supplied from the mother across its placenta and responds to the composition and balance of those nutrients. It monitors hormones produced by the mother, sometimes modified by the placenta, and then passed on to it. To a lesser extent, it detects gravity, light and dark, and sound levels. Certainly, if the mother becomes ill with an infection or develops a complication of pregnancy, such as high blood pressure or pre-eclampsia, the fetus will pick up signs of this problem. All this information is used to help the developing baby to adjust to the world in which he or she will live after birth. These signals coming from the mother may be very valuable to the survival of the baby as it grows and develops after it is born. The ‘decisions’ made by the fetus in adjusting its development are not, of course, conscious, but are intrinsic aspects of our biology—just as the pancreas ‘knows’ to secrete more insulin when we have high blood sugar levels.

As we develop, these sensing and control mechanisms get more sophisticated. They affect just about every organ of the fetal body in some way or another. We noted the number of urine filtering units in
the kidney, and the number of muscle cells in the heart, but they also regulate the density of the bones, the types of fibres in the major muscles of the body, the way in which the pancreas and the liver work to control metabolism, and even how the fetal brain and its later reproductive function will develop. It would appear that the fetus is using its time in the womb to educate itself about what its future life will be like. And the mother is doing her best to teach her fetus about the world in which she lives, on the assumption that this will be the world in which her baby will live too.

When we think of it in these terms, it is obvious that the developmental period of each human being has the potential to confer an enormous advantage on that person later on. Think of the different lives and experiences between an Inuit in Greenland and a Masai in Kenya, or even between someone who lives in a poor village in Uttar Pradesh and someone from the wealthy area of Malabar Hill in Mumbai—these differences could not be more stark. Being prepared for the way of life in these very different conditions will be an enormous advantage.

The better a growing baby is prepared to live in these different environments the better he or she will fare in later life. Being prepared is dependent on making use of the fact that our early development is to some extent plastic. Certain components of our development are, of course, fixed—we have four limbs and 20 digits, our heart is on the left, our thyroid gland makes thyroid hormones rather than adrenaline, and so on. But at a more subtle level there is plasticity in our development, such that subtle environmental changes in fetal and infant life influence many aspects of it. We may end up with finger lengths that are different, we may be taller or shorter, and we will have considerable variation in the number of heart and brain cells and in the sensitivity of the multiple control systems that operate our bodies.

But there is a cost. Because the fetus is sensitive to its environment, there are, unfortunately, circumstances in which the environment provided by the mother is damaging to its development. For example, if she takes the drug thalidomide between 20 and 40 days of pregnancy, the placenta turns that drug into a toxin that affects fetal limb development. That the placenta could turn drugs into poisons was, sadly, not known at the time that thalidomide was developed. Alternatively, sometimes infectious agents get across the placental barrier and damage the fetus; rubella (German measles) is a well-known example, but there are others, such as the bacterium listeria found in some unpasteurized cheeses, or the bacterium that causes syphilis. These agents interfere with the fundamental fetal developmental programme and cause significant disruption of both structure and function—with serious lifelong consequences.

Thankfully these cases of developmental disruption are relatively rare, and they are not our focus. What concerns us here is the range of environmental influences that can alter the pattern of essentially normal development. These are generally more subtle influences and reflect the common range of experiences that a mother might have—from what she eats to her general health or the degree of stress she experiences. Even without dangerous situations such as famine and starvation, sometimes the mother and placenta fail to deliver enough food, or the right balance of nutrients, to the fetus. Then the fetus has to make a decision—how should it allocate its scarce resources? Sometimes it ‘decides’ to reduce its body growth while maintaining energy supplies to its rapidly growing brain and heart. The result may be a fetus of reduced birth weight. Sometimes it decides to maintain the growth of its liver and to lay down more fat and less muscle. The result is a baby with a different body composition but probably no reduction in birth weight.

The fetal supply line of food is complicated—it is influenced by what the mother eats and her digestion, her reserves in the form of her body composition, her health, and her energy balance.
The nutrients leave her bloodstream and enter the placenta, which consumes some for its own needs and passes the rest on to the fetal bloodstream. The placenta’s metabolism is important for exchanging some vital nutrients such as essential amino acids with the fetus. Placental malfunction is common in pre-eclampsia, and that is why fetal growth retardation is often associated with this condition. But every fetus is dependent on its placenta, and the hormonal and metabolic dialogue between the two, about supply and demand, affects fetal development in ways that can have long-term consequences.