Natural experimental models: the global search for biomedical paradigms among traditional, modernizing, and modern populations.

During the past four decades, biomedical scientists have slowly begun to recognize the unique opportunities for studying biomedical processes, disease etiology, and mechanisms of pathogenesis in populations with unusual genetic structures, physiological characteristics, focal endemic disease, or special circumstances. Such populations greatly extend our research capabilities and provide a natural laboratory for studying relationships among biobehavioral, genetic, and ecological processes that are involved in the development of disease. The models presented illustrate three different types of natural experiments: those occurring in traditionally living, modernizing, and modern populations. The examples are drawn from current research that involves population mechanisms of adaptation among East African Turkana pastoralists; a search for etiology and mechanisms of pathogenesis of an emerging disease among the Yakut people of Siberia; and psychosocial stress, hypertension, and cardiovascular disease in women working outside the home in New York City and among subpopulations in Hawaii. The models in general, and the examples in specific, represent natural laboratories in which relatively small intrapopulation differences and large interpopulation differences can be used to evaluate health and disease outcomes.