THE HYDRATE MICROCRYSTAL THEORY OF GENERAL ANESTHESIA*

OR SIXTY YEARS the generally accepted F theory of anesthesia was the MeyerOverton theory or some variant of it. Meyer3 (1899) and Overton6 (1901) had independently observed that there is a rough correlation between the anesthetic activity of narcotic drugs and their solubility in fats, such as olive oil, and the suggestion was accordingly made that i t is the presence of molecules of the anesthetic agent dissolved in the lipids of the brain that is responsible for anesthesia. A similar rough parallelism is observed between the partition function of anesthetic substances between olive oil and water and their anesthetic activity. This “theory” was essentially an empirical correlation ; i t did not purport to provide an explanation or mechanism of anesthesia. In this respect, that of vagueness, the theory of anesthesia was, like theories of physiological activity in general a half century ago, essentially no different from theories of chemical structure and reactivity at t h a t time. However, after the development of powerful experimental methods of determining the structure of molecules and crystals (x-ray diffraction of crystals in 1913; electron diffraction of gas molecules in 1929 ; spectroscopic methods of determining the structure of molecules, about 1920; the theory of quantum mechanics in 1925; the theory of the chemical bond in 1927; the theory of van der Waals intermolecular attraction in 1929), chemistry began to change from a highly empirical and in some respects vague and even mystical science to a true science, including theories of structure in relation to the properties of substances that were powerful enough to give to the chemist a feeling of understanding of chemical phenomena on the basis of the structure of atoms and molecules.