1152 LINDQUIST that some creature living in the depths of the ocean does not have a heat-shock response, but that is doubtful. The proteins are induced by a wide variety of other stresses, seem to have very general protective functions, and may well play a role in nonnal growth and development. Man has long studied the effects of heat on himself and other living things, but studies of the heat-shock response per se began in 1962 with the publication of a little-noticed paper describing a new set of puffs on the salivary gland chromosomes of a fruit fly, Drosophila busckii, puffs induced by heat, di nitrophenol, or sodium salicylate (1). For the next decade the response was studied solely at the cytological level, but several important observations were made. Most notably, it was shown that the puffs were (a) induced by several other stress treatments (1-4),(b) produced within a few minutes (2, 3),(c) associated with newly synthesized RNA (1, 4),(d) found in other Drosophila species and in many different tissues (5, 6), and (e) accompanied by the disappearance of previously active puffs (2--4). In 1973, Tissieres & Mitchell inaugurated the molecular analysis of the response by reporting that the induc tion of these puffs coincided with the synthesis of a small number of new proteins (7). Investigations quickly shifted to Drosophila tissue-culture cells (8, 9), far more amenable to biochemical analysis, and the pace accelerated. From the first, the response was hailed as a model system for investigating gene structure and regulation. In this vein, investigations have proven ex tremely successful. The genes for the Drosophila hsps were among the first eukaryotic genes to be cloned (10-14), to have their organization within the genome defined (10, 13-22), to have their chromatin structure determined before and after activation (23-26), to have their regulatory sequences identi fied (27, 28), and to have the transcription factors interacting with these sequences characterized (29-33). Genes for one of the proteins, hsp70, pro vided one of the first convincing examples of gene conversion acting on an evolutionary time scale (34). The response also provided one of the first examples of selective gene expression operating at the level of translation (35, 36).

It was not until 1978-1979 that investigators, working on other organisms, discovered that heat and many other types of stress could induce the synthesis of similar proteins in cultured avian cells (37), in yeast (38, 39), and in Tetrahy mena (40). Within a few years similar responses had been reported in an extraordinary variety of organisms. Investigations of gene structure and regUla tion in these organisms are proceeding apace and several interesting lessons have already been learned. We now know that some heat-shock genes have been very highly conserved during evolution, not only in their protein-coding sequences (41--45), but also in their regulatory sequences (27, 41-48). Further more, it is now clear that the responses of different cells and organisms are regulated in different ways, reflecting their specific biological characteristics