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Symposium: Novel Concepts in the Developmental Origins of Adult Health and Disease

Developmental Plasticity and Evolutionary Biology^1,2

Sub-Department of Animal Behaviour, University of Cambridge, Madingley, Cambridge, CB3 8AA, UK

^* To whom correspondence should be addressed. E-mail: ppgb{at}cam.ac.uk.

	ABSTRACT

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Fetal experience determines some of the characteristics of human adults. Well-nourished mothers have offspring who are adapted to affluent conditions; mothers on a low level of nutrition have offspring who are adapted to lean environments. If the mother's forecast of her offspring's future environment is incorrect, the health of her offspring may suffer severely. The developmental plasticity that accounts for the ill health of humans who are living in conditions of rapid economic change is commonplace in biology. Understanding the evolutionary background sets the developmental origins of ill health in humans in context and has profound implications for public health.

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 (4) (Fig. 1). The triggering of normally appropriate modes of response gives us a fresh way of thinking about individual differences. To underscore the point, the extreme alternative view is that every one of us has a single ideal state on which we should all converge, given perfect nourishment, stimulation and so forth. Anybody who failed to achieve that state had made the best of a bad job and, at the margins of existence, expressed pathological stunting of body and behavior. One version of the general case that I wish to make is an idea developed by Waterlow about malnourishment of humans (5). He and others have suggested that, far from expressing the devastating effects of bad diet, small size, reduced metabolic rate, and reduced behavioral activity are all part of a suite of responses by humans to a world that does not have much food in it. Waterlow's suggestion was developed by Hales and Barker who referred to individuals with bodies and metabolisms adapted to a low level of nutrition as having a "thrifty phenotype" (6).

View larger version (13K): [in this window] [in a new window]   Figure 1  A given genotype may give rise to different phenotypes depending on the state of the environment early in development. Cues from the environment may be used a predictors, determining which of a set of alternative developmental pathways is elicited. If the environment does not change, then the organism's phenotype will be well adapted to that environment, providing a close match, as is represented in the diagram by the pattern and shape of the phenotype and the pattern and shape of the environment. However, if the environment does change between the elicitation of the particular pattern and development, then the phenotype may be mismatched to the conditions of adult life.

With respect to nutrition, the extended version of the hypothesis is that the pregnant woman unwittingly signals to her unborn baby that the environment her child is about enter is likely to be harsh. 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, thereby helping the child to cope with a shortage of food if the forecast is correct. These individuals, having small bodies and specialized metabolisms adapted to cope with meager diets, run into problems if, instead, they find themselves growing up in an affluent industrialized society to which they are poorly adapted (7).

The hypothesis about the fetal origins of adult disease deals well with the evidence provided by Barker and his colleagues (8), though not of course to babies who were born prematurely. Among a large group of individuals, who were born at term and breast-fed as babies, those who had the lowest weights at birth had the highest death rate from cardiovascular disease. The argument is that mothers on a low level of nutrition signaled to their unborn child that the environment outside would be harsh. As a result, the babies were born with the suite of adaptations that would have suited them well to diets low in carbohydrates and fat. However, they were poorly adapted to the affluent environment in which they subsequently grew up. Subsequently a great many other studies from around the world have supported this conclusion and shown that many other conditions such as type 2 diabetes are exhibited by people born small but subsequently reared on rich diets (9).

Natural experiments

The hypothesis that people have phenotypes that were developmentally elicited by their mothers' nutritional condition has led to a reexamination of what happens to people unlucky enough to have been born into an unusually harsh environment, such as those found during a war. Toward the end of the Second World War, the German occupation forces in the Netherlands cut off the food supplies coming into the northern part of the country. The population of much of the Netherlands suffered severe food shortages for 6 mo. When babies born to mothers who suffered particularly badly from starvation during the final 3 mo of their pregnancies 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 because they grew up in a nutritionally much richer, postwar environment (10). Whether contrived or natural, no experiment is perfect, of course, and some of the long-term effects could have been caused by other forms of deprivation associated with a period of starvation in late pregnancy. Nevertheless, the finding provides a strong hint of a sensitive period when a particular pattern of development might be set in train by the mother's nutritional state.

The opposite side of the coin is that people who grow up in good environments may be at greater risk during periods of prolonged famine than those who were born as low-birth-weight babies. Children born to affluent parents are more likely to suffer adverse effects if they are starved in adulthood. In concentration camps and the worst prisoner-of-war camps, anecdotal evidence suggests that the physically large individuals died first while at least some of the small individuals survived (7). In a famine-exposed Ethiopian population, higher birth weight was associated with a 9-fold higher risk of rickets (11). This might have been caused by the children with large bodies having higher needs for calcium and vitamin D than those with smaller bodies, but the point is that these children were at greater risk and had a lower chance of reproducing successfully than the smaller children.

Against "programming"

Those environmental influences with long-term effects on the adult phenotype are being described by an ever-increasing number of authors. These factors have been given an unfortunate name. They are described as "programming" the developing organism (12). At the 2005 Toronto conference on the Developmental Origins of Adult Health and Disease, I challenged the use of the term (13). On looking through the abstracts of the same conference, I noticed that every author who used the term "programming" in his or her title referred to cases where an environmental condition, usually a reduction in maternal nutrition, led to ill health or poor performance by the offspring growing up in an environment where food was provided freely. The programming metaphor is unfortunate in any event because it implies that instructions were provided by the environmental condition to which the individual had been exposed. Returning to the analogy with a juke –box, it would clearly be a mistake to suppose that a pressed button feeds a tune into the machine. Pressing a button selects a tune recorded beforehand. The current usage of "programming" seems to suggest that only when the level of nutrition in the environment is restricted are special adaptations brought into play. An environment in which unlimited supplies of food are available is likely to be highly abnormal in a natural environment. It would be much better to use a language that describes the development of alternative phenotypes that are usually appropriate to the conditions in which they appear. I suggest that a neutral term for the induction of developmental plasticity is "environmentally elicited."

The conventional clinical view has been that the consequences of early deprivation are pathological, just 1 part of the many damaging consequences of poverty. The argument from evolutionary biology is that the consequences should be viewed as deriving from 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 (5). If environmental conditions are bad and likely to remain bad, individuals exhibit adaptive developmental responses to those conditions.

Public health implications

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 (14). 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 overeating, some are consequences of the breakdown of economic order as in the former Soviet bloc, and some, mostly in Africa, represent the terrible effects of deteriorating local conditions. Analysis of trends to identify the supposed consequences of having a small phenotype in an affluent environment is vastly complicated by the widespread use of new drugs, such as those 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 demonstrated across the world, then the secular trends will continue, and the maladaptive consequences will disappear when maternal forecasts eventually become accurate.

Meanwhile, public health objectives would be, first, to encourage people who were born with low birth weights to eat a healthy, balanced diet, low in carbohydrate and fat relative to protein. 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 needs to be handled with care. If the children are adapted to a higher level of nutrition than would be normal in their society, then diet supplementation must be continued throughout their development.

Clearly, extreme malnourishment has pathological effects. Kwashikor resulting from extended periods of protein deficiency is seriously damaging to the individual. Even when development is not disrupted, the cost of coping with poor conditions at the start of life may have a long-term effect on physique and ability to reproduce (15). Despite the undoubted costs of seriously adverse conditions in early life, it is illuminating to treat the human body as the exquisitely well-designed thing that it is, capable of developing appropriately in response to a very wide range of environmental conditions. Instead of treating the body's responses to early deprivation as invariably pathological, these responses 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, as 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 inquiry and brings together clinicians and evolutionary biologists.

	FOOTNOTES

 
¹ Presented as part of the symposium "Novel Concepts in the Developmental Origins of Adult Health and Disease" given at the 2006 Experimental Biology meeting on April 2, 2006, San Francisco, CA. The symposium was sponsored by the American Society for Nutrition and the Danone Institute International. This supplement is the responsibility of the Guest Editors to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition. The Guest Editors for the symposium publication are Dennis Bier, U.S. Department of Agriculture/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates St., Houston, TX 77030 and Emanuel Lebenthal, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.

² Supported by The Leverhulme Trust and the Royal Society of London.

	LITERATURE CITED

TOP ABSTRACT LITERATURE CITED

 

1. Bateson P, Martin P. Design for a life: how behaviour develops. London: Jonathan Cape; 1999.

2. Bateson P. Biological approaches to the study of behavioural development. Int J Behav Dev. 1987;10:1–22.

3. Jablonka E, Lamb MJ. Evolution in four dimensions. Cambridge: MIT Press; 2005.

4. Bateson P, Barker D, Clutton-Brock T, Deb D, D'Udine B, Foley RA, Gluckman P, Godfrey K, Kirkwood T, et al. Developmental plasticity and human health. Nature. 2004;430:419–21.[Medline]

5. Waterlow JC. Mechanisms of adaptation to low energy intakes. In: Harrison GA, Waterlow JC, editors. Diet and disease in traditional and developing countries. Cambridge: Cambridge University Press; 1990. p. 5–23.

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

7. Bateson P. Fetal experience and good adult design. Int J Epidemiol. 2001;30:928–34.[Free Full Text]

8. Barker DJP. Mothers, babies and health in later life. Edinburgh: Churchill Livingstone; 1998.

9. Gluckman P, Hanson M. The fetal matrix. Cambridge: Cambridge University Press; 2005.

10. Ravelli AC, van der Meulen JHP, Michels RPJ, Osmond C, Barker DJ, Bleker OP. Glucose tolerance in adults after prenatal exposure to famine. Lancet. 1998;351:173–77.[Medline]

11. Chali D, Enquselassie F, Gesese M. A case-control study on determinants of rickets. Ethiop Med J. 1998;36:227–34.[Medline]

12. Lucas A. Programming by early nutrition in man. Ciba Found Symp. 1991;156:38–55.[Medline]

13. Bateson P. Against programming. Pediatr Res. 2005;58:1025.

14. United Nations Development Programme. Human development report. New York: Oxford University Press; 2000.

15. Gluckman PD, Hanson MA, Spencer HG, Bateson P. Environmental influences during development and their later consequences for health and disease: implications for the interpretation of empirical studies. Proc Biol Sci. 2005;272:671–7.[Abstract/Free Full Text]

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