been identified (Finnell et al., 2002). Presumably there are narrow windows of rapid development throughout childhood, including puberty, but critical windows of sensitivity to disruption have not been adequately described (Selevan et al., 2000). The complex interrelationships between genetics and environmental stimuli are not clearly defined and are an active area of current research.

Gene Expression

Understanding of the genome has rapidly expanded the study of the ways in which genes interact with diverse influences (e.g., physical and social environments) to affect health. Expression of genes (the amount of the protein encoded for by the gene) has a profound influence on the health of the individual. Gene expression is determined by many factors, such as promoters, regulators, mutagens/carcinogens/teratogens, X-inactivation, message stability, rate of protein degradation, prior exposures, all of which are affected by the environment. Interactions between genes and the environment influence different physiological pathways and adaptation (Holtzman, 2001) and may lead to adaptive or maladaptive phenotypes. An interesting example is the hygiene theory of childhood asthma, which postulates that children living in hygienic, low-pathogen environments develop an imbalance between two types of immune cell classes (TH1 and TH2). Children with an imbalance of TH1 and TH2 are more likely to develop allergies and asthma when confronted with allergens. When children live in low-hygiene, high-pathogen environments, they develop a strong system of immune regulators (a balance between TH1 and TH2 cells), and they are less likely to develop allergies or asthma (Yazdanbakhsh et al., 2002). Children living on farms or in homes with at least two cats or dogs in the first year of life have been shown to have significantly lower rates of allergic sensitization tested at 6–7 years (Ownby et al., 2002).

Healthy development depends on gene expression being responsive to changes in the environment. For example, the radical change in the environment at birth is responsible for changing the expression of genes to enable the baby to make the transition from intrauterine to extrauterine life. These include the production of proteins that close the ductus arteriosus (Kajino et al., 2001), alter lung liquid absorption (Matalon and O’Brodovich, 1999), produce barrier function in the skin (Harpin and Rutter, 1983), produce immunoglobulins, and alter gene expression in brain development. Thus, to be healthy, newborns must make profound changes in gene expression as they transition from intrauterine to extrauterine environments.

Converging findings from genetics and molecular biology demonstrate that a host of internal and external signals can stimulate or inhibit gene expression, including subtle factors such as the light-dark cycle (Hegarty, Jonassent, and Bittman, 1990) and tactile stimulation (Mack and Mack, 1992). This pattern of contingency is now recognized as part of the normal process of development in



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