HEINRICH WAELSCH t

On March 22, 1966, Heinrich Waelsch succumbed to a brain tumor, almost exactly a year after the diagnosis had been established. With his death neuroche- mistry has ]ost one of its most vigorous protagonists and most adventurous pioneers.

Heinrieh Waelseh was born on January 20, 1905, in Brno, Czechoslovakia. He graduated in Medicine at the German University of Prague in 1929 and obtained a doctorate in chemistry in the following year. The political convulsions of the thirties ended his career in Prague where he had reached the position of Privatdozent in the University Department of Biochemistry. I-Ie spent the rest of his life at Columbia University, New York, where he eventually became Profes- sor of Biochemistry and Chief of Psychiatric Research in the New York State Psychiatric Institute. I-Ie was a member of many societies, boards and committees and editor of several scientific ]ournals, among them Experimental Brain Research.

Although he had already more than 30 papers to his credit when he came to the U.S.A. in 1938, tIeinrich Waclsch first became known to a larger circle of physicians and biologists when he introduced the glutamic acid treatment of petit mal and mental deficiency. As is often the case, this t reatment was based on a rationale which later had to be abandoned, namely on the belief that the success of the treatment depended on the production of acidosis. Although the treatment was not always effective and the effects, if present, were often slight (as Waelsch was the first to admit) this piece of research had a dramatic impact on the prevailing atmosphere of fatalistic despair which surrounded the field of mental deficiency and blocked any active therapeutic approach. I t put Waelsch firmly on the road to the exploration of amino acid and protein metabolism in the brain. He developed sensitive methods for the microanalysis of glutamic acid and related substances and demonstrated the occurrence of high concentrations of glutamie acid in the central nervous system. He showed that glutamic acid administration does not lead to net uptake in the brain, in contrast to glutamine which is able to penetrate the blood brain barrier. On the other hand, he found that labelled glutamie acid rapidly exchanges with endogenous glutamic acid through the blood brain barrier; the latter thus was shown to permit, in this instance, rapid exchange but no net uptake. The observation that glutamine was synthesized in the brain from labelled precursors without extensive dilution by endogenous glutamic acid led him to the important concept of compartmentation, i.e. the existence of glutamic acid pools of different metabolic activity. In the

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presence of excess ammonia, glutamine is probably synthesized mainly from freshly synthesized glutamic acid rather than from glutamic acid already present in the tissue. Such a mechanism would soon lead to a depletion of dicarboxylic acids, were it not for the compensatory mechanism of carbon dioxide fixation. This latter reaction is thus a counterpart of the ammonia-binding reaction and its occurrence in nervous tissues has been studied intensively by Waelsch.

Another important concept of modern biochemistry whose development owes much to Heinrich Waelsch is the mechanism of group transfer. Waelsch came across this phenomenon when he observed the exchange of the amide group in ghitamine or asparagine with hydroxylamine or isotopic ammonia, catalyzed by the enzymes glutamo~ or asparto-transferase. An enzyme which has a similar effect but acts specifically on protein-bound amide groups is transglutaminase, discovered and studied by Waelsch and his group. Transglutaminase was found not only to bring about the exchange of amide groups with hydroxylamine or isotopic ammonia but also with a wide range of aliphatic amines which thus became incorporated into the acceptor protein. Another function of the enzyme was the formation of backbone bridges by the reaction of an e-amino group of protein-bound lysine with a protein-bound glutamine amide group. These reactions involve the elimination of ammonia; in addition the enzyme was found to be capable of hydrolyzing protein amide groups. I t therefore may be an essential component of the system responsible for the ammonia formation of animal tissues. Another example of group transfer established by Waelsch is the formation of the formyl derivative of tetrahydrofolic acid involving the transfer of a formimino group from a-l~-formamidinoglutarie acid which previously had been shown by Waelsch and associates to be an intermediate in histidine metabolism.

A major contribution of I-Ieinrich Waelseh to neuroehemistry was his demon- stration of the dynamic aspect of brain proteins. Far from being laid down once and for all, brain proteins have a turnover rate of a similar order to liver proteins as shown by the rate of incorporation of labeled lysine. Different proteins turn over at different rates : the proteins in the brain of the adult mouse have half-life times extending from about 3 to 15 days. Brain microsomes contain the most active protein fractions with half-life times of a few hours.

These are but a few highlights from a scientific achievement embodied in about 250 publications. In reviewing Heinrich Waelsch's writings one cannot help being struck by the breadth of his imagination and the range of his interests. His scientific tastes were indeed catholic and extended from organic chemistry to embryology, from enzymology to the learning process, from analytical methodolo- gy to the axonal flow and from bacteriology to behavior. Wherever possible he sought new syntheses: between morphology and biochemistry, between develop- ment and function, between change and equilibrium. He was a philosopher in addition to being a scientist and his mind was always probing for the deeper meaning. His many review articles and contributions to symposia and conferences attest to his originality and wisdom. Heinrich Waelsch was not only a successful and farsighted scientist, he also had a highly cultured mind of many facets and his knowledge of art, literature, history and philosophy was encyclopedic. This undoubtedly gave him the necessary perspective to see connections and corre- lations hidden beneath the surface.

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Those who were fortunate enough to know Heinrieh Waelseh, the man, will remember his charm and wit, his contagious enthusiasm and his warm generosity. He was a man of great sensitivity who enjoyed beauty in art and nature. He had a fundamental liking for his fellow men and his warm and open-hearted friendship was enjoyed by many. When he felt his help was needed he went out of his way to give it in unstinted measure. He was fond of good company and good company was bet ter when he joined it and contributed his gifts as causeur and conver- sationalist. He had the gift of being enchanted by simple things, amused and intrigued by small pleasures and able to wonder at familiar sights. For all his humility and unpretentiousness he was a shrewd judge of character. He did not suffer fools gladly and he delighted in deflating pomposity in any form. Yet his humor was wry and gentle and the barbs of his wit seldom hurt.

Heinrich Waelsch was a proud husband and father. Heinrich and Salome Waelsch were an unusual couple in tha t they were both scientists, both full university professors and both enjoyed an international reputation. To those who knew him well Heinrich's devotion to his family was one of his most touching and endearing qualities.

H. WEIL=MALII]~I~B]~ Clinical Neuropharmacology Research Center William A. White Building St. Elizabeths Hospital WASHINGTON, D.C.