Conclusions and comments for the XII ISCM.

The first International Symposium on Cholinergic Mechanism (ISCM), organized by the late Edith Heilbronn, was held in Skokloster in 1970; Alicante's XII ISCM shows the exponential progress made in the cholinergic field in barely 30 years! Thus, Alzheimer's disease was not a topic at the first ISCM. The concept of homeostatic mechanisms regulating choline levels in the brain was not conceived of as yet. Three-dimensional pictures and the the protein structure of cholinergic receptors were not even thought of, as in 1970, we had only an "abstract" knowledge of receptors, based on SAR notions of Everhardus Ariens, Robert Furchgott, and Peter Pauling; in fact the Nobel Prize winner Furchgott stated in 1964 that "... with rare exceptions, we cannot ... identify the receptor as an individual chemical entity." Similarly, three-dimensional images of cholinesterases (ChEs) and the ChE "gorges" were unknown (Furchgott, 1964). The Whittakerian notion of synaptic vesicular release of acetylcholine (ACh) was the only version of the mode of ACh release, and the unorthodox opinions of Yves Dunant, Maurice Israel, Bruno Ceccarelli and Jacopo Meldolesi were still to be promulgated. Little was known about cholinergic correlates of behaviors such as learning and aggression, and there was no notion of cholinergic aspects of self-awareness (consciousness), free will, and the active subconscious. And modern methodologies were unknown, including the measurements of ACh, such as the gas chromatography-mass spectrometry (GCMS) method, discovered by Israel Hanin, Don Jenden, and Bo Holmstedt in the 1950s, the chemiluminescence developed by Maurice Israel, Yves Dunant, and their associates (Israel et al., 1983), and crystallography and molecular biology techniques, such as the "knockout" (KO) mouse models.