The heat shock response in biology and human disease: a meeting review.

The heat shock response first attracted the attention of molecular biologists because it offered an attractive experimental system for studying a small set of coordinately controlled genes. Further study showed that the heat shock response was actually an important homeostatic mechanism, enabling the cell to survive a variety of environmental stresses. The fundamental nature of this mechanism is underscored by the fact that the heat shock response is found in all animals, plants, and bacteria. The heat shock response is essentially a single cell response and, even for multicellular organisms, can be studied with homogeneous populations of cultured cells, circumventing the complexities of interactions between different cell types. The many simple experimental systems for studying heat shock are yielding rapid advances in our understanding of the biology of both heat-shocked and normal cells; however, they have left open important questions about the role of heat shock in the complex physiology of multicellular organisms. For example, most animals have several mechanisms for regulating body temperature, ranging from the induction of fever to behavioral modifications. To what extent do changes in body temperature produce physiological effects by inducing the heat shock response at the level of individual cells? Answers to this question, among others, will undoubtedly be important in our understanding of disease. The importance of heat shock has been recognized for some time in the field of cancer therapy where hyperthermia is one component of treatment in many cases. For cancer therapy, the question is how best to overcome the heat shock defense of the cancer cell. To answer these questions will require expertise from a number of fields, including molecular and cell biology, physiology, ontology, and radiation biology. A recent Banbury Workshop, {November 9-13, 1987} organized by William Welch {Cold Spring Harbor Laboratory I and Richard Morimoto (Northwestern University} brought together a group of such specialists for the first time to consider the heat shock response. Several of the major themes that emerged from the Workshop are discussed below.