The experimental observations described in this article indicated that a distribution of many different fluctuations is present in a globular protein. These fluctuations were characterized by observation of many natural internal probes such as the labile peptide protons and the aromatic side chains. The conditions which are necessary to get reactions of the internal probes have been discussed in detail. The structural interpretation of the data was facilitated by the development and the use of new NMR techniques which provided the identification of the resonances of all the labile peptide protons. With NOE measurements a distinction between correlated and uncorrelated exchange events was obtained. This enabled us to elucidate the exchange mechanism over a wide range of p2H and temperature and to classify different subsets of fluctuations with respect to their lifetimes. It was further demonstrated that a change of external conditions such as temperature, p2H or pressure can change the distribution of fluctuations in the protein. The mechanisms responsible for rotation of internal aromatic side chains were also found to change with temperature, and mechanistic aspects of these fluctuations were discussed.

Piezoelectricity and pyroelectricity in wool and hair were observed by Martin early in 1941. The piezoelectric effect in wood was investigated in detail by Bazhenov (1961). Both converse and direct effect of shear piezoelectricity in wood was demonstrated by Fukada (1955). Bending piezoelectricity in bone was first discovered by Yasuda (1953). Shear and longitudinal piezoelectricity in bone and tendon was quantitatively investigatged by Fukada & Yasuda (1957, 1964).

We shall not attempt here to enumerate the results or review in a systematic way the significant literature dealing with the use of high pressure in studies of proteins and other molecules of biological interest. Two recent reviews on this subject, one by MOrild (1981) and another by Heremans (1982), and a further article by Jaenicke (1981) on enzymes under extreme environmental conditions contain expositions and references that would render redundatn such a task. Rather we concentrate here on the examination of othe conceptual framework employed in the interpretation of high pressure experiments and in the critical discussion of our knowledge of selected areas of present interest and likely future significance.