Fetal experience and good adult designa

Patrick Bateson

Sub-Department of Animal Behaviour, University of Cambridge, Cambridge, UK.

Professor PPG Bateson, The Provost's Lodge, King's College, Cambridge CB2 1ST, UK.

Keywords Adaptation, design, development, evolution, low birthweight, thrifty phenotype, maternal induction, alternative lives

Accepted 1 June 2001

Biology is the study of complicated things that give the appearance of having been designed for a purpose. This thought has been articulated most clearly in recent years by Richard Dawkins,1 but it has been expressed in various ways for 200 years. A traveller finding a watch on a mountain path would not fail to attribute the quality of its design to human agency. A great British naturalist and theologian, William Paley2 regarded the design he saw everywhere in nature as proof of the existence of God. These days, the design to which Paley referred would instead be attributed by most biologists to blind Darwinian evolution. The form and behaviour of individuals vary within the same species and, in any given set of environmental conditions, some individuals may be better able to survive and reproduce than others because their distinctive characteristics are particularly well suited to those conditions. If their characteristics are inherited, then an ever increasing number of individuals in the population will be better adapted to that environment than was previously the case.

Plant and animal breeders have known for years how to select artificially the characteristics which they prized for one reason or another. Darwin called the blind evolutionary process leading to the appearance of good design ‘natural selection’.3 His phrase was popular in the 19th century because it suggested an agent for evolution. These days many biologists prefer to focus on the processes. What generates variation in the first place? What leads to differential survival and reproductive success? What genetic and environmental factors enable individual characteristics to be replicated in subsequent generations? While each of these questions raises separate issues, it is worth keeping in mind the idea of the evolutionary outcome—apparent design.

Environmental triggers

After a fire on the high grassland planes of East Africa, the recently hatched grasshoppers are black instead of being the normal pale yellowish-green. Something has switched the course of their development onto a different track. The grasshopper's colour makes a big difference to the risk that it will be spotted and eaten by a bird as the scorched grassland may remain black for many months after a fire. So matching its body colour to the blackened background is important for its survival.

The developmental mechanism for making this switch in body colour is automatic and depends on the amount of light reflected from the ground. If the young grasshoppers are placed on black paper they are black when they moult to the next stage.4 If they are placed on pale paper, however, the moulting grasshoppers are the normal green colour. The grasshoppers actively select habitats with colours that match their own. If the colour of the background changes they can also change their colour at the next moult to match the background, but they are committed to a colour once they reach adulthood.

Turtles and crocodiles and some other reptiles commit themselves early in life to developing along one of two different developmental tracks and like grasshoppers, they do so in response to a feature of their environment. Each individual starts life with the capacity to become either a male or a female.5 The outcome depends on environmental temperature during the middle third of embryonic development. If the eggs from which they hatch are buried in sand below 30°C, the young turtles become males. If, however, the eggs are incubated at above 30°C they become females. Temperatures below 30°C activate genes responsible for the production of male sex hormones and male sex hormone receptors. If the incubation temperature is above 30°C, a different set of genes is activated, producing female hormones and receptors instead. It so happens that in alligators the sex determination works the other way around, such that eggs incubated at higher temperatures produce males. (In humans and other mammals, by contrast, the sex of each individual is determined genetically at conception; if it inherits only one X sex chromosome it becomes male.)

Each grasshopper and turtle starts life with the capacity to take one of two distinctly different developmental routes—becoming green or black, male or female. A particular feature of the environment determined the path taken by the individual for the rest of its life, and once committed, the individual cannot switch to the other route. Once black as an adult, the grasshopper cannot subsequently change its colour to green, just as a male turtle cannot transform itself into a female.

The broad pattern of an individual's social and sexual behaviour may also be determined early in life, with the individual developing along one of two or more qualitatively different tracks. Many examples are found in the animal kingdom. The caste of a female social insect is determined by her nutrition early in life. The main egg producer of an ant colony, the queen, is part of a teeming nest in which some of her sisters care for her offspring, others forage, yet others clean or mend the nest, and finally other sisters specialize in guarding it.6

The sexual behaviour of some primates can also develop along two or more distinctly different tracks. An adult male gelada baboon, for example, will typically defend and breed with a harem of females. After a relatively brief but active reproductive life, he is displaced by another male and never breeds again. To position himself so that he can acquire and defend a harem, the male must grow rapidly at puberty. He develops the distinctive golden mane of a male in his prime and becomes almost twice the size of the females.7 However, when many such males are present in the social group, an adolescent male may adopt a distinctly different style of reproductive behaviour. He does not develop a mane or undergo a growth spurt. Instead, he remains similar in appearance and size to the females. These small males hang around the big males' harems, sneakily mating with a female when the harem-holder is not paying attention. Since the small, sneaky male never has to fight for females, he is likely to have a longer, if less intense, reproductive life. If he lasts long enough he may even do better in terms of siring offspring than a male who pursues the alternative route of growing large and holding a harem. It is believed that these two different modes of breeding behaviour represent two distinctly different developmental routes, and each male baboon must commit himself to one or other of them before puberty.7

In each of the above cases, the individual animal starts its life with the capacity to develop in a number of distinctly different ways. Like a jukebox, the individual has the potential to play a number of different developmental tunes. But during the course of its life it plays only one tune. The particular developmental tune it plays is triggered by a feature of the environment in which the individual is growing up—whether it be the colour of the ground, the temperature of the sand, the type of food, or the presence of other males. Furthermore, the particular tune emanating from the developmental jukebox is adapted to the conditions in which it is played.8 Many other examples can be given.9,10 The juke-box analogy has its drawbacks because it implies the tune is pre-formed somehow; like everything else, the expressed phenotype has to develop.11 The analogy with ‘programming’12 is even worse because it implies that the environmental trigger contains the instructions for the phenotype that will be expressed. The term ‘imprinting’13,14 has a somewhat similar defect. Perhaps, the best general term for the processes is an old one used in development biology for many years, namely ‘induction’.

The implication of many of the phenomena described here is that environmental induction provides a prediction about the conditions of the world which the individual will subsequently inhabit. In mammals the best route for such a forecast may be via the mother. Vole pups born in the autumn have much thicker coats than those born in spring; the cue to produce a thicker coat is provided by the mother before birth.15 The value of preparing in this way for colder weather is obvious. Maternal forecasting by induction is likely to be very important in human biology.

Human development

Is it the case that people, like grasshoppers or baboons, are conceived with the capacity to play a number of qualitatively different developmental tunes—in other words, to live alternative lives? Each of us started life with the capacity to live many different lives, but each of us lives only one. In one sense individual humans are obviously bathed in the values of their own particular culture and become committed by their early experience to behaving in one of many possible ways.

Differences in early linguistic experience, for example, have obvious and long-lasting effects. By the end of a typical high school education, a young American will probably know about 50 000 different words.16 The words are different from those used by a Russian of the same age. In general, individual humans imbibe the particular characteristics of their culture by learning (often unwittingly) from older people. When environmental conditions induce a particular developmental route in animals, the mechanisms involved are likely to be different; learning may not enter into the picture at all. Is it possible that some aspects of human development are triggered by the environment, as though the individual were a jukebox? Was each of us conceived with the capacity to develop along a number of different tracks—to live a number of distinctly different sorts of life? And does the environment trigger the particular developmental track that each of us follows?

The now famous series of studies, led by David Barker, assessed people across their entire lifespan from birth to death.17 This work has lent strength to the suggestion that human development may also involve environmental cues that prepare the individual for a particular sort of environment. Those men who had had the lowest body-weights at birth and at one year of age were most likely to die from cardiovascular disease later in life. Those born as the heaviest babies enjoyed a much reduced risk of dying from cardiovascular disease. It was only half the average for the group as a whole, whereas the risk for the smallest babies was 50% above average (in other words, three times greater than that for the largest babies). Individuals who had been small babies were also more likely to suffer from diseases such as non-insulin dependent diabetes and stroke in adulthood. The analogies with rats are striking. When pregnant mother rats are given restricted diets, their offspring are smaller and when given plenty of food they become much more obese than the offspring of mothers given an unrestricted diet.18

How could a link have arisen between a man's birthweight and his physical health decades later? The evidence pointed to a connection with the mother's nutritional state. Women with poor diets during pregnancy had smaller placentas, and 40 years later their offspring had higher blood pressure (a risk factor for cardiovascular disease and stroke).17 But the links with maternal nutrition went much further back than pregnancy. Measurements of the mothers' pelvises revealed that those who had a flat, bony pelvis tended to give birth to small babies. These small babies, after they had grown up, were much more likely as adults to die from stroke.17 The implication was that poor nutrition during their mother's childhood affected the growth of her pelvis which, in turn, curtailed the growth of her offspring during pregnancy which, in turn, increased her offspring's risk of stroke and cardiovascular disease in adulthood.

The evidence took a surprisingly long time to be accepted given that nobody had doubted that environmental conditions early in development have a significant impact on many other aspects of human biology, including size. People are getting bigger.19 For decades now, the average height of men and women in industrialized countries has been steadily increasing. Although some of the height differences between people are due to genetic differences, the general trend for average height to increase is almost certainly due primarily to improvements in nutrition and, to a lesser extent, health. Hence, successive generations of the same family have grown taller despite having a similar genetic make-up.

The average size of men in the UK has been increasing at about one centimetre per decade.20 In Russia, where the improvements in nutrition have occurred more recently, the rate of increase in height lagged behind Britain but has been at almost three times the rates found in Britain in the last few decades.21 That means an increase of 3 cm a decade. In the US the trend towards ever taller offspring in successive generations, which started earlier than in Britain, has levelled off in recent years. These findings suggest an upper limit on the effect of nutrition on human height. It is noteworthy that the effects of improved nutrition on height have been much more pronounced in men than in women.20

The average age of puberty (as marked by the sudden slowing of growth that occurs shortly after puberty) has declined more rapidly in girls than it has in boys.19 This sex difference in the changing age of puberty has therefore worked in the opposite direction to that of height, where men have become relatively taller. Why has the age of puberty in girls apparently responded more rapidly to nutritional improvements than it has in boys? It may not be necessary to invoke an adaptive explanation. Girls develop sexually earlier than boys, so it could be that when nutritional conditions are bad, girls are simply forced to develop later and the gap between boys and girls is thereby reduced. Needless to say, another hypothesis accounts for the sex difference in adaptive terms.

In a rich environment well supplied with food, females are able to start having children earlier in their lives. Females who responded to the nutritional conditions by starting to reproduce earlier would have more offspring than females who did not respond to those cues. Individuals who were equipped with the developmental flexibility to adjust the timing of their sexual maturation in response to environmental conditions would be at an advantage. This would set in train an evolutionary trend to establish a jukebox-like developmental response to the quality of the environment. The developmental rule would be: if conditions are good, become sexually mature early; but if conditions are poor, delay maturity. The developing male, on the one hand must therefore strike a balance between starting to breed as early as possible and developing the physical capacities to cope with competition from other males. A developing male who channelled all his resources into accelerating his sexual development, at the cost of remaining smaller and weaker, would be less well equipped to compete with other males. Without the physical size and maturity, a sexually precocious male would be unable to compete with adult males, and would suffer in the process of trying. An optimum balance is struck when the young male has grown to a reasonably large size before he becomes sexually mature. This adaptive analysis fits the observation that good conditions have led to a larger acceleration in sexual development in females than in males.

These associations between environmental conditions, body sizes and mating systems raise some provocative questions about humans. Is the type of marriage system found within a culture correlated with the difference in size between men and women in that culture? And is monogamy more common in societies living in harsh environments where food is in short supply? At first glance, the answer is disappointing, since the ratio of male to female height is roughly the same in both monogamous and polygamous human societies. However, a clear difference does emerge when monogamous societies are divided up into those in which the marriage system of monogamy is imposed by ecological conditions, and those found in more affluent conditions where it is socially imposed, in the sense that it is a requirement of the culture. Men and women living in harsh environments where life is a struggle, such as the high Arctic and the edges of deserts, are more similar in size than those living in easier circumstances, and they are more likely to be monogamous.22 This supports the adaptive hypothesis that in poor conditions, a monogamous man caring for the offspring of one woman is more likely to have surviving children and grandchildren than a polygamous man who has children by many women.

The thrifty phenotype

Poor maternal physique and health are associated with reduced fetal growth, with consequences for the offspring's later health. The question arises, then, as to whether these connections make sense in adaptive terms. Could it be that, in bad conditions, the pregnant woman unwittingly signals to her unborn baby that the environment which her child is about enter is likely to be harsh? (Remember that we are thinking here about what might have been happening tens of thousands of years ago as these mechanisms were evolving in ancestral humans.) And perhaps this weather forecast from the mother's body results in her baby being born with adaptations, such as a small body and a modified metabolism, helping the child to cope with a shortage of food. This hypothetical set of adaptations has been called the ‘thrifty phenotype’.23,24 Perhaps these individuals with a thrifty phenotype, having small bodies and specialized metabolisms adapted to cope with meagre diets, run into problems if instead they find themselves growing up in an affluent industrialized society to which they are poorly adapted. That, at least, is the hypothesis.

People who grow up in impoverished conditions tend to have a smaller body size, a lower metabolic rate and a reduced level of behavioural activity.14 These responses to early deprivation are generally regarded as pathological—just three of the many damaging consequences of poverty. But they could also be viewed as part of a package of characteristics that are appropriate to the conditions in which the individual grows up—in other words, adaptations to an environment that is chronically short on food, rather than merely the pathological by-products of a bad diet. Having a lower metabolic rate, reduced activity and a smaller body all help to reduce energy expenditure, which can be crucial when food is usually in short supply.14 If environmental conditions are bad and likely to remain bad, individuals exhibit adaptive developmental responses to those conditions.

Now this conjecture might well be regarded as offensive. It could be seen as encouraging the rich to look complacently at their impoverished fellow human beings, by arguing that all is for the best in this best of all possible worlds (as Voltaire's Doctor Pangloss would have had it). Merely to assert that every human develops the body size, physiology, biochemistry and behaviour that is best suited to their station in life would indeed be banal. The point, however, is not that the rich and the poor have the same quality of life. Rather, it is that, if environmental conditions are bad and likely to remain bad, individuals exhibit adaptive developmental responses to those conditions. To put it simply, they are designed to make the best of a bad job.

Defending nutritional targets

It is worth bringing in here some more animal work. It has been known for many years that if a pigeon is deprived of both food and water, and then given a choice, it will alternate between choosing food and water.25 The animal efficiently compromises between meeting a variety of target requirements. Exactly the same point applies to the various constituents of food. Stephen Simpson and his colleagues have suggested how the animal defends a combination of food constituents that provides the best balance for itself.26 For simplicity, suppose that the target diet for an individual is 50% carbohydrate and 50% protein. If it is given a choice of two diets one of which contains 25% protein and 75% carbohydrate and the other 75% protein and 25% carbohydrate, then the animal will switch its preference from one diet to the other. The overall effect is that it gets 50% protein and 50% carbohydrate.

If the animal is given a single diet containing the wrong combination relative to the target balance, it will reduce its intake to minimize the risk of imbalance. To be more accurate, many animals will do so—but with exceptions that are highly relevant to the matter in hand. A particularly interesting case is the desert locust—one of the most famous cases where a single species exists in various phenotypes, the extremes of which are a solitary phase and a gregarious phase. The expression of the phenotype depends on population density.27 The phases at their extremes are strikingly different in their behaviour, appearance and physiology28—so striking, indeed, that at one time they were treated as different species.

The solitary form is a shy, cryptic animal only flying at night. Typically, it lives at low densities and avoids other locusts except to mate. However, when the population starts to become more dense, the appearance and the behaviour start to change, taking several generations to complete the full transition to the other form. The fully formed gregarious phase looks strikingly different. These animals aggregate with each other. They form enormous swarms that fly in daylight. These swarms can contain hundreds of millions of insects per square kilometre and consume hundreds of thousands of tons of vegetation per day. These terrible plagues can extend over 57 countries and cover more than 20% of the land surface of the Earth.27

The two forms differ in the way they eat. The gregarious form is a generalist, consuming a wide variety of vegetable matter of different compositions. The gregarious form can expect to balance its diet because it is on the move through a heterogeneous environment, eating everything it comes across. The solitary form has little opportunity to rebalance and has to be more careful.

Simpson and his colleagues29 have shown what happens when the two phases are given an unbalanced diet. The solitary form utilizes its diet more efficiently and with less cost to itself. It incorporates a higher proportion of the protein it ingests into its body. Furthermore, it is more likely to survive until the end of its period of growth.

Obviously this intriguing story cannot be generalized lock, stock and barrel to the human case. But it does raise important questions about human behaviour and physiology that may be relevant to why small babies are more likely at the other end of their lives to die from heart disease in an affluent environment. The people with the thrifty phenotype may be like the gregarious locust in the sense that, when they are given an unbalanced diet, they fail to regulate properly and do not achieve their dietary targets so readily. It would be possible to test this possibility in a non-invasive way using the elegant techniques of Simpson and Raubenheimer.26

Babies with thrifty phenotypes growing up in an affluent environment may be effectively poisoned and therefore operate sub-optimally. Some recent research found a strong correlation between cognitive abilities and low birthweight.30 Rather than treating this as further evidence of pathology, it is possible that these people have been polluting themselves with an inappropriate diet. The effects of a diet to which they are not well adapted could have non-specific effects. These people with thrifty phenotypes could become lethargic with shorter attention spans and perform poorly in cognitive tests in an affluent environment. Here again, the hypothesis can be tested.

Why don't individuals adapt to local conditions in their own lifetimes? The image of the adaptive landscape used by Sewall Wright31 in evolutionary biology may be helpful here. His thought was that in the same environment individuals with different gene combinations might be equally well adapted (on equally high mountains using his image), but that going from one mountain to another entailed a loss of fitness. Engineers and economists dealing with optimization problems often find local optima, knowing full well that better solutions can be found. In the context of the evolutionary adaptive landscape, an organism may reach the top of one mountain. While it might be beneficial to cross over to a higher mountain, getting from a low mountain top to a higher one, involves going downhill before climbing once again. The same image may be used in development. Once a phenotype is fully formed, it may be difficult to switch to another phenotype that has become more beneficial because of a change in local conditions.

A number of important conclusions have emerged from studies of sensitive periods in development.8 Although the use of a common term like ‘sensitive period’ should not imply a common underlying mechanism, it does draw attention to the basic fact that all forms of experience are not equally important at all stages in development. A body, once built, is difficult to alter. Making fundamental changes to mature behaviour patterns or personality traits will similarly take time, resources and quite possibly support from others. Adults have important tasks to carry out, such as feeding and caring for their family, and cannot readily dissolve themselves and re-construct their behaviour without others to care for them during the transition phase.

Accumulating evidence

The thrifty phenotype hypothesis has led to a re-examination of what happens to people unlucky enough to have been born into unusually harsh environments, such as those found in a war. Towards the end of the Second World War, the German occupation forces in The Netherlands cut off the food supplies coming into the country. The population of much of The Netherlands suffered severe food shortages for six months. Babies born to mothers who suffered particularly badly from starvation during the final three months of their pregnancies were born with low birthweights. When these babies grew up, their capacity to deal with high levels of sugar was markedly reduced, as would be expected if they were adapted to a world containing little sugar. One undesirable consequence for these individuals was an increased risk of developing diabetes, since they had actually grown up in a much richer, post-war environment.32 Another was that women who had been fetuses in the last third of pregnancy during the famine gave birth to children with lower birthweights than normal.33 This second-generation effect is important when considering the big differences in heart disease between adjacent countries.

The siege of Leningrad (now St Petersburg) by the German army in the Second World War lasted from the autumn of 1941 until the end of January 1944 and was one of the most gruelling sieges in history. The Germans, having invaded the Soviet Union in June 1941, approached Leningrad and almost completely encircled the city by September 1941, cutting off nearly all of its supply lines. The resulting starvation and disease, combined with German shelling, killed 650 000 of its inhabitants in 1942 alone. What happened to people who were born during the siege of Leningrad? Fifty years later, three groups of people were compared: those whose mothers had suffered from malnutrition while they were pregnant during the siege; a second group born in Leningrad just before the siege began, who experienced starvation during their infancy; and a third group born at the same time but outside the siege area.34 No differences were found in the incidence of heart disease or diabetes between those whose mothers had been starved during pregnancy and those who were themselves starved in infancy. This result is still consistent with the thrifty phenotype hypothesis, since the nutritional state of people in Leningrad after the Second World War was generally poor compared with people living in the West. It could be argued that the mothers' nutritional weather forecasts, made to their unborn children during the siege, were on the whole reasonably accurate. Furthermore, although some people among all three groups grew into obese adults, those whose mothers had been pregnant during the siege had higher blood pressure than obese people in the other groups. This suggests again that they were less well adapted to a world markedly different from that of their fetal life—a world in which food was in rich supply.

The thrifty phenotype hypothesis suggests a novel explanation for another observation that has long puzzled nutritionists. People living in France have significantly less ischaemic heart disease than people living in northern European countries. The difference is particularly noticeable when France is compared with Finland. The two countries have comparable average intakes of dietary cholesterol and saturated fat, yet the mortality from heart disease in Finland has for decades remained about four times higher than that in France for both sexes. From 1986 to 1994 the average standard death rate was 354 per 100 000 men per year in Finland and 94 in France.35 It seems unlikely that such a large difference can be explained simply in terms of the different methods of classifying heart disease in the two countries. Nor does a difference in general health seem plausible as an explanation. Indeed, over the 1986–1994 period the average standard death rate from infectious diseases and parasites was 8 per 100 000 men per year in Finland and 12 in France.35

Popular explanations for the differences between Finland and France have focused on nutritional differences such as the intake of red wine.8 However, in the context of maternal forecasting, an intriguing possibility is raised by the recent histories of the two countries. Until the end of the Second World War, Finland was a very poor country, but since then it has acquired a high standard of living. If a poor forecast during pregnancy prepares the developing offspring for a poor environment, while a good forecast prepares the individual to cope with a fatty diet later in life and the effect may carry over two generations, heart disease in Finland should start to fall in about 2015. What about France? After the Franco-Prussian War, the French were concerned that they were becoming a third class military power and wished to produce stronger children.36 Accordingly, the French government supplemented the rations of pregnant mothers about 50 years before any other country introduced such measures. Allowing 20 years for the 1880 batch of babies, which received a forecast of affluent conditions, to grow up and another 50 years for them to reach the age when heart disease is likely to strike, the incidence of heart disease should have started to decline in 1950 and continue to fall as the second generation effects started to kick in. With the improvement of nutritional conditions in other parts of Europe, the mothers' forecasts will increasingly correspond to reality and heart disease should drop to the low levels reported in France.

If the thrifty phenotype hypothesis is correct then the massive social experiment of the one-child policy in China could produce ill effects, arising from a mismatch between body and environment. The only-children resulting from the Chinese government's policy tend to be bigger, heavier and better nourished. But many of these children have been born to mothers who had low birthweights and thrifty bodies. If the thrifty phenotype idea is correct, the children may be at great risk from the diseases of affluence.

By the same logic, people who grew up in good environments may be at greater risk during periods of prolonged famine than those who were born as low birthweight babies. And perhaps children born to affluent parents are more likely to suffer adverse effects if they adopt rigorous diets in adulthood. In German concentration camps, anecdotal evidence suggests that the strong died while at least some of the weak survived.37 After the capturing of the Sixth Army at the end of the siege of Stalingrad in 1943, chances of survival of the German prisoners of war was low. Beevor reports: ‘The first to die were generally those who had been large and powerfully built. The small thin man always stood the best chance’.38

The public health implications of the thrifty phenotype hypothesis are profound. From 1970 to 1997 the change in nutritional intake has been dramatic. In the tables of available data given in the United Nations report on development, 38 countries have gone down, but 106 have gone up.39 Three-quarters of the countries of the world have increased their average energy intake per capita. Of those that have gone down, some are countries where people have started to gain control of over-eating, some are due to the breakdown of economic order as in the former Soviet bloc and some represent the terrible effects of deteriorating local conditions. Analysis of trends in the various supposed consequences of having a thrifty phenotype in an affluent environment is vastly complicated by the widespread use of new drugs that control blood pressure, for example. This might explain the declining incidence of coronary heart disease in most developed countries despite the increasing incidence of obesity. If it remains possible to sustain the heightened standard of living which has been demonstrated across the world, then the secular trends will continue and the maladaptive consequences disappear when eventually maternal forecasts become accurate. Meanwhile, public health objectives would be, first, to encourage people who were born with low birthweights to eat a healthy diet. Second, moves should be made to supplement during pregnancy the diets of those small mothers whose children are likely to grow up in an affluent environment. Supplementing the diets of those mothers whose children are likely to remain in a thrifty environment would be counter-productive.

Conclusion

The general point is that humans, like many other animals, are capable of developing in different ways and, in stable conditions, their characteristics are well adapted to the environmental conditions in which they find themselves. The cues for the way in which the individual develops is provided during sensitive periods early in development. The mechanisms are largely to be discovered.40,41 Generally such systems of developmental plasticity work well, but in a changing environment they generate poorly adapted phenotypes because the environmental forecast proved to be incorrect. The argument may be generalized to the effect of a human mother on her unborn child in the last three months of pregnancy. The condition of the mother in late pregnancy may be taken to provide a forecast about the state of the environment in which the child will grow. This then determines the pattern of growth and the metabolic pathways of the child. If the mother's forecast was wrong, the consequences for the child can be dire. The hypothesis is that the under-nourished mother gives birth to a child who is small in size and is adapted to a thrifty environment. Conversely a well-nourished mother gives birth to a large baby who is adapted to an affluent environment.

Clearly, extreme malnourishment has pathological effects. Kwashikor resulting from extended periods of protein deficiency is seriously damaging to the individual. However, it is illuminating to treat the human body as the exquisitely well-designed thing that it is—capable of responding to a very wide range of environmental conditions. Instead of treating the body's responses to early deprivation as invariably pathological, they should be viewed as part of a package of characteristics that are appropriate to the conditions in which the individual grows up—in other words, adaptations to an environment that is chronically short on food. This is not an empty Just-So Story, but a hypothesis that suggests many new lines of enquiry.



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Photography: Mary Shaw

 
Notes

a Based on ‘Design for Living’, an address given at the First World Congress on Fetal Origins of Adult Disease, Mumbai, India, 3 February 2001. Back

References

1 Dawkins R. The Blind Watchmaker. London: Longman, 1986.

2 Paley W. Natural Theology: or, Evidences of the Existence and Attributes of the Deity, Collected From the Appearances of Nature. London: Faulder, 1802.

3 Darwin C. The Origin of Species. London: Macmillan, 1859.

4 Rowell CHF. The variable coloration of the Acridoid grasshoppers. Advances in Insect Physiology 1971;8:145–98.

5 Bull JJ. Sex determination in reptiles. Q Rev Biol 1980;55:3–21.[ISI]

6 Wilson EO. The Insect Societies. Cambridge, MA: Harvard University Press, 1971.

7 Dunbar RIM. Reproductive Decisions: An Economic Analysis of Gelada Baboon Social Strategies. Princeton: Princeton University Press, 1985.

8 Bateson P, Martin P. Design for a Life: How Behaviour Develops. London: Vintage Paperbacks, 2000.

9 Caro TM, Bateson P. Organisation and ontogeny of alternative tactics. Animal Behav 1986;34:1483–99.[ISI]

10 Lott DF. Intraspecific Variation in the Social Systems of Wild Vertebrates. Cambridge: Cambridge University Press, 1991.

11 Oyama S, Griffiths PE, Gray RS. Cycles of Contingency: Developmental Systems and Evolution. Cambridge, MA: MIT Press, 2001.

12 Horton TH, Stetson MH. Maternal programming of the fetal brain dictates the response of juvenile siberian hamsters to photoperiod—dissecting the information-transfer system. J Exp Zool1990;(Suppl.4):200–02.

13 Patel MS, Vadlamudi SP, Johanning GL. Overview of pup in a cup model—hepatic lipogenesis in rats artificially reared on a high-carbohydrate formula. J Nutr 1993;123(Suppl.S):373–77.[ISI][Medline]

14 Waterlow JC. Mechanisms of adaptation to low energy intakes. In: Harrison GA, Waterlow JC (eds). Diet and Disease in Traditional and Developing Countries. Cambridge: Cambridge University Press, 1990, pp.5–23.

15 Lee TM, Zucker I. Vole infant development is influenced perinatally by maternal photoperiodic history. Am J Physiol 1988;255:R831–38.[Abstract/Free Full Text]

16 Pinker S. The Language Instinct. New York: Morrow, 1994.

17 Barker DJP. Mothers, Babies and Health in Later Life. Edinburgh: Churchill Livingstone, 1998.

18 Jones AP, Friedman MI. Obesity and adipocyte abnormalities in offspring of rats undernourished during pregnancy. Science 1982;215:1518–19.[ISI][Medline]

19 Eveleth PB, Tanner JM. Worldwide Variation in Human Growth. Cambridge: Cambridge University Press, 1990.

20 Huh DL, Power C, Rodgers B. Secular trends in social class and sex differences in adult height. Int J Epidemiol 1991;20:1001–09.[Abstract]

21 Dubrova YE, Kurbatova OL, Kholo ON et al. Secular growth trend in two generations of the Russian population. Hum Biol 1995;67:755–67.[ISI][Medline]

22 Alexander RD, Hoogland JL, Howard RD et al. Sexual dimorphisms and breeding systems in pinnipeds, ungulates, primates, and humans. In: Chagnon NA, Irons W (eds). Evolutionary Biology and Human Social Behaviour. North Scituate, MA: Duxbury, 1979, pp.402–35.

23 Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992;35:595–601.[ISI][Medline]

24 Hales CN, Desai M, Ozanne SE. The thrifty phenotype hypothesis: how does it look after 5 years? Diabetic Med 1997;14:189–95.[ISI][Medline]

25 McFarland DJ, Sibly R. ‘Unitary drives’ revisited. Animal Behav 1972; 20:548–63.[ISI][Medline]

26 Raubenheimer D, Simpson SJ. Integrative models of nutrient balancing: application to insects and veterbrates. Nutr Res Rev 1997;10:151–79.[ISI]

27 Simpson SJ, McCaffery AR, Hägele BF. A behavioural analysis of phase change in the desert locust. Biol Rev 1999;74:461–80.[ISI]

28 Pener MP, Yerushalmi Y. The physiology of locust phase polymorphism: an update. J Insect Physiol 1998;44:365–77.[ISI][Medline]

29 Simpson SJ, Raubenheimer D. Assuaging nutritional complexity: a geometrical approach. Proc Nutr Soc 1999;58:779–89.[ISI][Medline]

30 Richards M, Hardy R, Kuh D et al. Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study. Br Med J 2001;322:199–203.[Abstract/Free Full Text]

31 Wright S. Genic interaction. In: Burdette WJ (ed.). Methodology in Mammalian Genetics. San Francisco: Holden Day, 1963, pp.159–92.

32 Ravelli ACJ, van der Meulen JHP, Michels RPJ et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998;351:173–77.[ISI][Medline]

33 Stein Z, Susser M, Saenger G et al. Famine and Human Development. New York: Oxford University Press, 1975.

34 Stanner SA, Bulmer K, Andres C et al. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross-sectional study. Br Med J 1997; 315:1342–49.[Abstract/Free Full Text]

35 Eurostat. Yearbook ‘97: A Statistical Eye on Europe. Luxembourg: Office for Official Publications of the European Communities, 1997.

36 Law M, Wald N, Stampfer M et al. Why heart disease mortality is low in France: intrauterine nutrition may be important. Br Med J 1999; 318:1477–78.[ISI][Medline]

37 Steinberg P. Speak You Also: A Survivor's Reckoning. London: Allen Lane, 2001.

38 Beevor A. Stalingrad. London: Viking, 1998.

39 Programme, UND. Human Development Report 2000. New York: Oxford University Press, 2000.

40 Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr 1999;69:179–97.[Abstract/Free Full Text]

41 Chapman C, Morgan LM, Murphy MC. Maternal and early dietary fatty acid intake: changes in lipid metabolism and liver enzymes in adult rats. J Nutr 2000;130:146–51.[Abstract/Free Full Text]