Fat, Fate, and Disease : Why we are losing the war against obesity and chronic disease (18 page)

Maternal stress can affect the fetus because when stress hormone levels are high, they can overwhelm the normal mechanisms that limit their passage across the placenta. The levels of the stress hormone cortisol (which is made by the adrenal glands) are normally tightly regulated, and the fetus generally has very low levels of cortisol until late in gestation, when its production by the fetus starts to increase in the run-up to birth. Babies born prematurely do not have high enough cortisol levels and this makes their survival risky, because the hormone prepares the fetus for birth by maturing organs such as the lungs. This discovery in the 1970s was arguably the most important in neonatal medicine. Sir Graham (Mont) Liggins in Auckland found that an artificial form of cortisol could bypass the placental barrier and, when given to a woman in premature labour, would accelerate her baby’s lung maturation. Overnight, the survival of many premature babies became possible. Much modern neonatal medicine is based on refinements of this discovery, which has saved hundreds of thousands of lives.

The causes of premature labour are poorly understood. One common cause is infection which can ascend from the vagina and pass through the protective membranes around the fetus, releasing chemicals that initiate labour. The fetus in this situation is better out of the dangerous infected environment, and so ‘makes’ the choice to be born prematurely, to have at least some chance of survival. In evolutionary terms this trade-off
could only have worked for a small degree of prematurity—perhaps only after a pregnancy duration of 37 weeks or so.

Other causes of premature delivery reflect the conditions of the mother early in pregnancy. We now know that mothers who are inadequately nourished at this time are more likely to give birth a few weeks prematurely. Indeed, across the developing world pregnancy lengths are often one to two weeks shorter than in the developed world. As we shall see, this brings with it a cost. We also know that mothers who experience severe stress, such as surviving an earthquake, have a shorter length of pregnancy. But the surprising finding is that it is those women who suffered the traumatic experience in early pregnancy who have the earlier births. The fact that gestational length is influenced by events in early pregnancy suggests that the tempo of fetal development is set in early embryonic life.

Some simple experiments make this point very clear. Farm animals such as sheep often give birth to twins, or even triplets, and every sheep farmer knows that these will be smaller than singleton animals. For many years it was thought that this was because nutrient supply, and even physical space, was less for each fetal lamb if a twin or triplet than if they had the uterus, the mother, and the placenta to themselves. But then a researcher, Frank Bloomfield in Auckland, decided to ask a very simple question. At what rate would a twin sheep fetus grow if its other twin was removed or died in early gestation? Would it grow at the same rate as a singleton fetus, as it now had no competition, or would it grow at the rate of a twin, as it was actually conceived? The answer was clear and surprising—the surviving twin still grew at the rate of a twin, as if it did not know that it had its mother’s resources all to itself. Clearly, aspects of fetal growth and development are established very early in pregnancy.

So embryos and fetuses use information derived from the mother to predict what kind of nutrition they will receive or how much stress they will be exposed to after birth. They then use the fact that development is plastic or flexible to shift the set points in their metabolic
and stress control systems so as to be better placed to thrive in the world into which they predict they will be born. They will not get it right all the time and, as we will see, this has consequences. But as they
do
get it right more often than not, evolution has preserved these plastic mechanisms. Practically all multicellular organisms have some form of a developmental phase, and in every type of animal studied so far (and indeed in many plants too), developmental plasticity is used to establish a strategy to optimize fitness from early on in the life-course.

What is the meaning of such a life-course strategy? Quite simply, that we can’t do everything in our lives to perfection and so it is necessary to make choices to concentrate more on certain aspects and less on others. In other words we have to make trade-offs, and the most powerful ones which all complex organisms make are between investing resources for reproduction as opposed to investing them in the repair and maintenance necessary for longevity.

We need to examine this idea. Does it mean that a developing organism should invest all available resources in its future reproduction? And what do we mean by reproduction? The answer is not as simple as investing in sperm and egg machines. Successful reproduction is about much more. We must survive to and through sexual maturation; we must attract an appropriate mate; and we must survive long enough for our offspring themselves to be independent and reproduce—otherwise our genes will not persist, and, in evolutionary terms, that is what life is about.

Accordingly, the balance of survival and reproductive strategies varies enormously between animal species. But every one has a strategy which balances successful reproductive potential against the contingencies of the ecological niche in which the species finds itself. Critical phases of our evolution occurred in Africa five to six
million years ago, when we diverged in our ancestry from the other great apes, and then perhaps 160,000 years ago when modern Homo sapiens first emerged. Of our last 160,000 years—which equates to perhaps 8,000 generations—most was in the so-called Palaeolithic period. Agriculture and settlement only appeared 10,000 years ago (some 500 generations) in the Middle East, and more recently elsewhere. This was the Neolithic period. But in contrast to these long periods of our evolutionary past which shaped our biology, many of the issues we are concerned with in this book relate to the last 100 years—the last four generations or fewer.

While we can only speculate about the patterns of reproductive behaviour in our Palaeolithic ancestors, anthropologists have enough clues to arrive at a consensus. First, females would have mated soon after puberty. Those women in better nutritional condition would be more likely to survive; those who were of larger build would be less likely to have an obstructed labour. Males probably competed for females either by social dominance, for example by being head of the clan, or possibly by sheer physical dominance over other males. In many hunter-gatherer societies physical prowess determines social dominance, so we can surmise that strong and large males had a greater role in creating the human gene pool in the Palaeolithic period.

In evolutionary terms, survival up until the time of reproduction is critical for both males and females. It is pointless to come to within a few months of achieving puberty and then succumb to an infection or an injury. So we have evolved with a strategy such that our growing bodies also invest considerable resources in repair and defence mechanisms, whether they are the processes of immunity by which we fight off invading bacteria and viruses or the processes by which damage to our DNA is repaired following the accidents which happen to it during cell division. But doing this effectively up to the time of reproduction leads to a trade-off against having as much capacity to do so later in life.

The balance between how much resource to invest in growth and reproductive function and how much to invest in repair and restoration later in life is thus a classic life history trade-off. The important point is that the equilibrium involved in this trade-off can be shifted if environmental circumstances change. This has been extremely well demonstrated in many animal species. For example, many amphibians, such as the spadefoot toad, will trade off between growth and the timing of metamorphosis from a tadpole into an adult if they are challenged with harsh environmental conditions. Suppose that the pond in which the tadpoles are living in the Arizonan desert begins to dry up. Clearly it is time to leave the pond and make the best of it on land. So the metamorphosis of the tadpoles is accelerated, and they become young toads in order to leave the pond. As a result, they become reproductively competent at a younger age even though they are smaller as adult toads. This is a risky strategy because smaller animals are more likely to be picked off by predators such as snakes or birds but it is a gamble that has to be taken if there is to be any chance of reproduction. To stay as a tadpole when the pond has dried up is certain death. It is no good waiting to grow to a certain size before reproducing if waiting will be fatal.

There is a range of threatening situations in life which can evoke a similar strategy. For example, in guppies (the little fish often seen in aquaria) that live in the wild, the presence of high numbers of predators induces early puberty in the male guppy. These guppies reproduce early and abundantly, even though they are small, and are then likely to die earlier.

And it looks as if humans do the same thing as well. Puberty can be best studied in females, as the age at the first period, or menarche, is a reliable and clear measure of sexual maturation. A study by a number of anthropologists of modern hunter-gatherer communities has looked at the age at menarche and related it to the likelihood of mortality at a young age in those communities. These hunter-gatherer societies are small groups of people in the Amazon, New Guinea, and Central Africa who have lives somewhat similar to
those who lived before modern technologies and colonization. Of course their lives are not exactly as they were 2,000 years ago, and often they have been displaced from their ancestral homes, but this study does give us some insights into Neolithic society and biology. It turns out that in those societies, where there is a high risk of juvenile death, the age at menarche can be as much as six years earlier than in those societies where the juvenile mortality is low.

But if the decision is made to reproduce early, and this must be at the cost of the body’s growth and repair systems, what might be the longer-term consequences? For the spadefoot toads it is a greater risk of death by predation. But what about humans? As we discussed in the last chapter, while our expected lifespan—except in the least developed world—is now in the order of seven to nine decades, in our evolutionary past most individuals probably lived no more than three to five decades. And it was through those 8,000 generations of the Palaeolithic that our biology evolved. It was ‘designed’ to make trade-off decisions about surviving to reproduce and to support our children until they reached the age of independence. We estimate that this meant that we evolved to live for about 35 to 50 years.

How did we arrive at this figure? The best evidence comes from the study of female reproduction. By the age of 35, even well-nourished healthy women in the most developed societies show a decline in fertility—the chances of getting pregnant even with unprotected intercourse at the optimal time in the menstrual cycle starts to decline. In most women, by the age of about 50 the ovaries have ceased to release eggs altogether and menopause occurs. In hunter-gatherer societies menopause tends to be closer to 40 years. Presumably, in evolutionary terms women by that age are likely to have had sufficient children—even though up to half of them may have died—to sustain the lineage. Following the cessation of reproduction, women in early human societies would have had to survive for at least another decade to support their youngest child to reproductive maturity. If the youngest child was a girl, there may have been a further evolutionary advantage in the
woman surviving long enough for her grandchildren to reach maturity. This suggests an evolved average life expectancy of around 50 years of age. Males, on average, enter puberty later than females and have shorter lives, but examination of modern athletes suggests that males in early human societies would most likely have had peak physical performance in their thirties. Probably many of them did not live much beyond this age.

Clearly most of our Palaeolithic ancestors did not die of old age, although some of them did live well into their later years. We imagine that senile dementia, Alzheimer’s disease, or even the fractured hips of the elderly, regrettably so common today, were a rarity then. Most deaths, presumably, occurred from infection and injury through accident or violence. Death in childbirth was also common—perhaps affecting 10 per cent of all women. In any event we did not evolve to live even the three score years and ten quoted in the Bible. This may explain why the common chronic non-communicable diseases which we associate with ageing today—cancer, cardiovascular disease, stroke, dementia, and osteoporosis—are so difficult to treat. All of these diseases have a pathological component which results from an inability to repair damaged biology.

So we can see the result of the trade-off: in order to achieve reproductive success earlier in our lives, we evolved the biological strategy of trading off the repair and restoration processes which we will need in middle and old age. The gamble paid off in terms of human evolution and colonization of the world, but every older person now has to pay the price.

The data on the hunter-gatherers we described earlier in this chapter give compelling evidence that trade-offs between reproduction and ageing actually exist in humans. But can we find other evidence? One way of looking at the problem is to see if there are historical records which allow us to relate reproductive success to lifespan in Western
populations over a long period of time. Do such records exist? Tom Kirkwood and his colleagues in Newcastle focused on the records that have been kept for the English aristocracy. In view of the importance of succession in the British royal family, it is clear that even several hundred years ago such records would be accurate as they would not have been for other members of society. In addition, we imagine that at any time in history the royal family has had access to the best available nutrition and so, if the biological trade-offs operate in this family, we would expect them to be less obscured by other complicating factors. Kirkwood and colleagues found that such trade-offs do indeed exist.