The role of clinical investigations in biological markers research.

As the agenda of the occupational and environmental health community proceeds from the study of the effects of high doses of toxins causing grossly altered disease patterns to examination of the impact of lower doses on prevalent disorders, new scientific approaches have become necessary. The emerging concept of molecular epidemiology, substituting biologically determined markers of dose and early effect for traditional measures of exposure and morbidity, offers a heuristically appealing direction for the field. However, the transition to this evolving approach has been slow and its potential has yet to be validated. In this essay, some of the limitations of this approach are discussed and theoretical modifications developed. The central proposition is that existing modalities of clinical research, widely employed in subspecialty medicine research but heretofore unexploited in the study of environmental diseases, offer great promise. By incorporating clinical investigations centrally, some historically rate-limiting problems such as variability of host responses, multiplicity of environmental risks, and differences between human and animal responses could be transformed from major impediments at present to realistic objects for future study.