Alex Karczmar - Scientific Achievements

Scientific Achievements

Karczmar published some 400 research papers, reviews and book chapters. He authored, co-authored or edited 7 books. His text, Exploring the Vertebrate Central Cholinergic Nervous System (Springer, New York, 2007) reviews the past and the present status of central cholinergicity, its physiology, pharmacology and biochemistry, its ontogeny and phylogenesis, and its role in functions, behaviors (including cognition), the "self" and such disease states as schizophrenia and Alzheimer's Disease; also, this text describes his own studies of these subjects.

His scientific contributions are as follows. In the 1940s Karczmar proposed the existence of a nerve growth factor on the basis of his demonstration of the quantitative effects of partial ablations of the urodele limb innervations on their post-amputation regeneration (Karczmar, 1946). Beginning in the 1940s Karczmar pioneered the studies of anticholinesterase agents (antiChe's), discovering (with Theodore Koppanyi; see Koppanyi and Karczmar, 1951) the direct synaptic effects of organophosphorus (OP) antiChEs which are independent of their enzymic block, their morphogenetic (teratologic) effects and their postnatal behavioral actions resulting from their prenatal application. He also demonstrated that the OP antiChe's damage the blood–brain barrier. These studies contributed to the understanding of the role of cholinesterases as morphogens and "transport" or "scavenger" enzymes (Karczmar et al., 1951).

This research led Karczmar to conceptualize on the pre-neurogenetic appearance of components of the cholinergic system, their non-parallel ontogenesis and its significance, and their omni-existent phylogenesis which is independent of the presence of innervation or motility (Scudder and Karczmar, 1966); see also Karczmar, 1963 a and b).

Karczmar and Steve Thesleff demonstrated in the 1950s the phenomenon of desensitization (receptor inactivation) at the neuromyal junction, and Karczmar described the reciprocal process, sensitization which is inducible by several drugs such as oxamides and NaF, and which, today, is ascribed to an allosteric receptor change (Karczmar, 1957; Karczmar and Howard, 1955). Karczmar pioneered also the studies of the structural nature of central cholinergic receptors by demonstrating the structural similarity between peripheral and central muscarinic receptors (Karczmar and Long, 1958).

With Kyozo Koketsu, Syogoro Nishi and Nae Dun Karczmar identified in the 1950s and 1960s the three ganglionic receptor sites (nicotinic, muscarinic and peptidergic) and their potentials; they described their ionic mechanisms and the contribution of second messengers to ganglionic transmission (see Karczmar et al., 1986).

Since the 1960s, Karczmar contributed to establishing the pre-eminent role of the central cholinergic system in functions such as respiration, behaviors such as aggression (Karczmar, 1973; Karczmar and Scudder, 1969a), perceptions such as nociception (Koehn et al., 1979), learning (Karczmar and Scudder, 1969b), addiction (Karczmar et al., 1978), obsession and fixation, and sexual and motor activity (Karczmar and Koehn, 1980; Karczmar, 1980), and in phenomena such as seizures (Karczmar, 1974), EEG rhythms, paradoxical sleep, and behavioral and EEG alerting (Karczmar et al., 1970); and he and his associates provided early neurochemical evidence for the interaction between the cholinergic and other transmitter systems (Glisson et al., 1972).

Karczmar demonstrated that cholinergic agonists counteract the behavior exhibited in animal models of schizophrenia (Karczmar and Richardson, 1985; Karczmar, 1988); on this basis and on the basis of other cholinergic behavioral and EEG actions Karczmar proposed that the cholinergic system contributes significantly to alertness, cognitive behavior and to the animal's (and human) "realistic" appraisal of the environment; he named the pertinent syndrome the "Cholinergic Alert Non-mobile Behavior" (CANMB; see Karczmar, 1979, 2007 and 2009).

Since the 1970s Karczmar explored the "self" (the "I", the self-awareness, the self-consciousness; see Karczmar, 1972 ); he traced the concept of the body-mind relation to the earliest history of mankind, millennia before the advent of Descartes' dualism. He stressed the need to differentiate the "self" from cognition and perception. While he is a reductionist, he suggests that the current neuroscientific and quantal stage of knowledge is insufficient to yield an intelligible and parsimonious explanation of the "I", and he speculates that with the future success of Einstein's quest for the single equation for all the forces of the universe the nature of "I" will become explainable, perhaps via multidimensional string theory(see Karczmar, 2007 and 2009).