The evolution of correlative techniques for electron microscopy--an overview.

The papers presented at this Pfefferkorn Conference demonstrate the dramatic recent progress in the science of biological specimen preparation for electron microscopy. This progress results largely from increased use of more diverse, critical, correlative scientific methods. This paper outlines several strategies that tend to promote this type of scientific approach, and that have proven generally useful in biological research. The strategy most commonly chosen to augment both the empirical and the cross-disciplinary components of structural studies is the correlative use of diverse experimental techniques on samples which are parallel to those prepared for microscopy. This type of approach tends to advance our understanding of biological structure and function and also of the scientific methodology. Such approaches redirect attention to the biological problem under study and tend to open new areas of investigation. A second strategy which promotes more rigorous scientific approaches is the application of correlative techniques to identical structures. In contrast with parallel studies, data from identical structures document directly the coincidence of different features within each individual structure, and these data establish the distributions of these features in the study population based on relatively few observations. A third strategy to promote more critical science is to utilize the effects of the specimen preparation as experimental parameters by varying the preparative methods with appropriate controls. This approach is especially valuable in studies of biological specimen preparation, where the potential impact of systematic errors warrants especially rigorous scientific practice.