Drugs for Mental Ills - C&EN Global Enterprise (ACS Publications)

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RESEARCH

Drugs for Mental Ills Serotonin deficiency may have important role in schizophrenia and other related mental disorders Three phases of modern life are creating an environment which is unsuitable for the furtherance of science, said newly reelected academy president Detlev W. Bronk. In his annual report he listed them as: fear of an uncertain future, exploitation of fear and misunderstanding "by those w h o seek selfish or unwholesome ends," and lack of understanding about t h e nature and objectives of science. Bronk urges scientists not to take passively an u n w a r r a n t e d attack on themselves or their professions, but rather suggests that they fight back hard wherever justified. Solar " F r a c t i o n a t i o n " Described. Additional physico-chemical data in support of t h e "low temperature" theory of formation of the solar system was presented b y H. C. Urey, University of Chicago. Variation in densities of certain planets and existence of two different groups of meteorites indicate t h a t a "chemical fractionation , , of iron from other nonvolatile constituents occurred during formation of the solar system. In addition, Urey concludes that there is no evidence of any important loss of elements less volatile than mercury from meteorites or from the earth during formation. For elements of greater volatility than mercury, there is some evidence of loss. H e points out that the state of oxidation of iron and other elements in t h e meteorites and t h e earth shows t h a t these materials probably w e r e not heated w h e n in contact with cosmic gases. These and other d a t a suggest to Urey that the.solar system might have been formed at extremely low temperatures, perhaps in the r a n g e of —220° C. He postulates that asteroidlike objects m a y have existed in dust clouds before the solar system was formed. The sun or a large star passing through the cloud might "capture" the asteroidal bodies, which would then revolve about the central star. While Urey admits there is no actual evidence for the existence of such bodies, h e says the possibility cannot b e entirely excluded. P e p t i d e s t o Proteins. There is evidence that some of the simple peptides can be utilized in tissue protein synthesis, according to Paul R. Cannon, Laurence E. Frazier, a n d Randolph H. Hughes, University of Chicago. Their Science. findings may h a v e an important prac-

W A S H I N G T O N . - A suggestion that mental disorders can b e treated with the high blood pressure hormone serotonin was made by D . W . Woolley and Elliott Shaw of t h e Rockefeller Institute at the annual meeting of t h e National Academy of Sciences. Animal tests indicate that such mental ills as schizophrenia may be caused b y a cerebral deficiency of serotonin, according to the authors. This conclusion is based on studies of several antiserotonin compounds. Such antimetabolites of serotonin as yohimbine and the ergot and harmala alkaloids, together with several synthetic analogs of the hormone, were prepared for the tests. Among each of these classes of compound, w h i c h inhibit the action of serotonin in body tissues, are substances which can cause mental disorders. T h e Rockefeller studies suggest t h a t the mental changes caused b y the drugs result from a serotonin deficiency which the drugs induce in t h e brain. T h e disorders induced by t h e antiserotonin drugs are similar to naturally occurring mental ailments. In t h e case of the natural ailments, however, the researchers say lack of serotonin may arise from a metabolic failure, rather than a drug action. Overcoming serotonin deficiencies may aid in treatment of such disorders. Woolley and Shaw believe t h a t serotonin has an important function in normal mental health processes. T h e y say they have gone as far as they can with biochemical and pharmacological findings. Now it is the task of clinical experimenters to determine possible value of serotonin treatments. This task may not b e an easy one, from preliminary indications. T h e first problem to be overcome is difficulty in getting serotonin into brain tissues. Experiments in animals reveal that serotonin injected peripherally fails to penetrate into t h e desired part of the brain. Consequently, a compound which has serotoninlike activity, but which will penetrate to the desired site, m a y have to b e found. Another possibility is the value of spinal injections of the hormone or its chemical relatives. This might enable the compounds to by-pass the "bloodb r a i n " barrier, which blocks certain substances carried in the blood from reaching cerebral tissue. Unsuitable 1876

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tical bearing o n use of protein hydrolyzates in nutrition. Protein synthesis is commonly assumed t o result from utilization of amino acids within cells, they point out. Some scientists also believe this process is quite rapid, with all t h e essential amino acids utilized practically simultaneously at the point of synthesis. T h e Chicago workers set out to determine whether peptides can b e utilized in a similar way. Past research had shown that protein hydrolyzates vary considerably in p e p t i d e content. There also is evidence t h a t peptides introduced into the blood stream may he excreted b y the kidneys, before they could take part in protein synthesis. It was not known, however, whether all peptides behaved similarly. In their tests on protein depleted rats, t h e researchers injected subcutaneously a mixture of 16 amino acids. The rats were also fed a "nonprotein ration" w h i c h was a d e q u a t e in roughage, calories, vitamins and salts. On such a diet, t h e rats w e r e able to synthesize protein and regain weight. B u t w h e n a single amino acid was omitted from t h e diet, weight loss quickly followed. It w a s possible, however, to substitute a synthetic p e p t i d e quantitatively for t h e appropriate essential a m i n o acid without loss of nutritive potency. Six synthetic peptides were used in the tests: glycyl-L-tryptophan, glycylL-leucine, glycyl-DL-phenylalanine, D L alanyl-OL-phenylalanine, DL-alanyl-DLmethionine, and leucyl-glycylglycine. The Flagella's Helix. Studies which shed n e w light on t h e structure of flagella, the whiplike protein organisms attached to bacteria, w e r e reported in another paper b y L. W . L a b a w and V. M. Mosley, Institutes of Health. Klectron micrographs of flagella of an unidentified Gram-negative bacteria show t h e flagella's external contour to be a double helix. Each of the flagella has a diameter of about 150 A. and appears to b e a tightly wound counterclockwise helix of a 130 A.-diameter fiber. T h e pitch of the helix varies between 25 and 35 degrees. Th' 1 bacterium used in the tests was a contaminant found in a bottle of India ink. T h e organism probably was present as a contaminant in the water used to make the ink. T h e cell wall of this bacterium is composed a t least in part of a membrane that shows no regular structure on its outside surface, the workers say. It does have a rectangular arrangement with a periodicity in each direction of about 115 A. on its inside surface. T h e thickness of the m e m b r a n e appears to b e about 7 5 A. AND

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