Structural determinants of disease and their contribution to clinical and scientific progress

The recognition of structural correlates with disease provided a release from the Hippocratic humors which dominated the approach to medicine for more than a thousand years. During recent decades an increasingly reductionist approach to structure has enabled such correlations to extent from those easily visible to the naked eye to those who resolution requires sophisticated electron microscopy. Although recognition of clinical--pathological correlations has evident advantages, there are instances, such as diabetes mellitus, where such recognition appeared to lull investigators into believing that the pathogenic mechanisms underlying the disease had been found. Moreover, the recognition of a structural abnormality, such as the extra chromosome in Down syndrome, may sometimes have delayed rather than accelerated research on metabolic aspects of the disease. The advances in medical understanding that have proceeded from a correlation of structure with function have enabled diseases to be investigated at different levels. This has led to a more sophisticated redefinition of the meaning of clinical--pathological correlations and to the surprising finding that immense structural variability can be tolerated by the human organism without its function being recognizably perturbed. Indeed, some molecular variations of structure lead to a distinct biological advantage under singular environmental conditions. Finally, where molecular structure is known in its most intimate detail, the distinction between structure and function becomes less easy to discern.