research summaries for teachers RAINER FRIED
Neurochemistry: A Preview Modern textbooks of biochemistry allot generally one chapter to chemistry of the nervous system, and one or two lectures are usually reserved for this topic in medical biochemistry courses. I n recent years, neurochemistry has taken gigantic strides, and much progress has been made in this field and in the related fields of neuropharmacology and psychopharmacology. Role of the Nervous System
When we attempt to define the chemical role of the organs of the body in terms of engineering chemistry we can derive the following grossly simplified scheme: Own Liver Heart Lungs Kidneys Digestive system
Funelion. Metabolic factory Liquid pump Gas exchange Filtration Comminution
It can be seen that the brain and spinal cord (central nervous system, CNS) and the nerves reaching from the spinal cord to all portions of the body (peripheral nerves) have different functions from those listed above. It can he stated that-again in simplified terms-the role of the nervous system is mainly that of communication and control, by means of electrical currents. The role of the nervous system thus is both more abstract and subtle than that of the other organs. Whereas the other organs carry out mainly chemical or mechanical functions, the action of the nervous system is electrical. The nervous system controls the functioning of all other parts of the body, by means of electrical signals. Although the exact mechanism of the generation of these electrical signals and their transmission along the nerve fibers is not yet fully cleared up, it is quite clear now that the electrical nerve impulses depend on very specific and extremely rapid chemical reactions within the nervous system. We require here a special knowledge concerning the transformation of biochemical information into electrical information. (In general terms, many of the other biochemical reactions occurring within the body and within each cell deal with the translation of biochemical events into energy storage or depletion.) - -
E D I ~ R NOTE: 's While Professor Fried's Research Summary is designed to provide an introduction to and a. prognostic overview of newoehemistry for the laymtm, his paper to appear in the May issue is a definitive summary of several important facets of this exciting new division of
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Conversely, the nervous system responds to many physical stimuli; these can be electrical or other types which first must be translated into electrical signals and then in turn are translated into biochemical reactions. The chemical basis of the physiology of nerve action is a relatively new concept, which met with considerable scepticism and resistance hut is now universally accepted. Much remains yet to be clarified in this area, in spite of the very great amount of research dedicated to this topic. It is difficult to pick scientists who made the most significant contributions to the biochemical basis of nerve activity; probably the most significant contributions have been achieved by Lowi, Dale, and Nachmansohn. Chemistry and the Mind
The brain thus controls the function of the whole body by means of electrical signals generated by specific chemical reactions. I n addition to this paramount activity, the brain carries out much more significant functions on a much more complex plane. I refer here to the role of the mind: intelligence, reason, behavior, memory, learning. It is becoming clear that these functions can be correlated with biochemical events occurring in the brain; they can also be influenced by chemical agents such as drugs and poisons. On an even higher plane--as yet far removed even from initial understanding-we have even more complex functions of the mind: character, personality, creativity, and morals. Based on the current march of science, it is a reasonable assumption that even these high functions will eventually be correlated with biochemical events. We shall come to the point where we will be able to correlate definite biochemical parameters with traits of character, and where genius can be explained in terms of small biochemical differences in well-circumscribed sections of the brain. I cannot say that this perspective makes me happy; I have quite ambivalent feelings about this. Understanding of matters of the mind in strictly biochemical terms lies far in the future; yet I am convinced that the day will come when this correlation can he made. On the one hand, I rejoice in the advance of science and progress made in expanding knowledge and understanding. On the other hand, the possibility of explaining strange and awesome mysteries in rational and even in numerical terms, creates a sadness and a sense of loss. I felt the same loss on a lower plane when I learned that the magnificant color scheme of foliage in Fall is simply due to destruction of the green chloroVolume 45, Number 3, March 1968
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phyll, with resulting prevalence of yellow and red carotenes and anthocyanins. To preserve the enjoyment and satisfaction caused by a beautiful autumn landscape, the scientific knowledge of its causes must be pushed into the background of the mind, and even blotted out. I expect that the same mental separation of knowledge of the underlying mechanism will have to be applied in the future, when we admire human greatness. Promise for the Future
With few exceptions, correlation between biochemistry and metabolism on the one hand, and somatic disease on the other, is a recent knowledge. To give just a few examples for this inter-relation between biochemistry and disease, we can list: deficiency diseases and vitamins; diabetes and insulin; gout and purine metabolism; cancer and deletion of enzymes found in normal tissues. It is probable that all disease can be explained in terms of abnormal biochemical reactions occurring in the diseased state and causing its manifestations. LIFE is the controlled interaction of enzymatic processes. .R. Willstktter DISEASE is the perturbation of the ~egdntedinteraction of enzymes. . . .R. Abderhalden
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I n these cases, much research remains to be done, and in most of them biochemical understanding is still in its infancy. Yet on the other hand, significant understanding has been gained, and important practical results derived, from this lcnowledge. Thus it is possible to cure diseases such as deficiency diseases and to control endocrine imbalance by administration of vitamins and hormones. What has been achieved in relation to somatic disease, and what promises to be achieved in the future, will also be true for disease of the mind. Just as knowledge of the biochemistry of the nervous system lags behind our understanding of the metabolism of the other organs, so does the understanding of mental disease in chemical terms follow behind understanding of disease of the body. During the progress of science, many currently accepted ideas met with scepticism and hostility, and it took considerable time for these ideas to gain universal credence. An interesting retrospect about the function of vitamins and their relation to deficiency disease has been published.' Just as the biochemical causation of disease had frequently been rejected by clinicians and internists, so was correlation between mental disease and biochemical events within the brain opposed by psychiatrists and psychologists. Yet success in this area is quite clear, although of very
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recent date. This area of research is really just developing, and the near future will bring many important new insights. Hallucinations and other symptoms similar to those found in schizophrenia can be produced by administration of drugs, some obtained from natural sources, others made in the laboratory; nervous depression and excitation can be related to alterations in brain metabolism. Behavior can be affected by administration of chemical reagents which produce welldefined chemical changes. Initial attempts have been successful to influence learning and memory by chemical means. Many investigators are studying the chemical composition of diseased brains and hope to be able to identify new and abnormal metabolites in mental disease. Thus the requirements of the nervous system, and the structures in which the nerve impulse is carried, such as nerve fibers and synapses, require also special chemical reactions. The unique tasks and problems of the nervous system function, which are not duplicated elsewhere in the body, also call for a special system of biochemical reactions. Therefore, the study of these reactions and the specific compounds involved justify an autonomous designation: although we do not speak of "hepatochemistry" or %ardiochemistry," the classification of this branch of biochemistry as "neurochemistry" seems amply justified. This said, it should be made quite clear that neurochemistry is a branch of biochemistry. The same classes of compounds exist in the brain as exist in other parts of the body. The same types of reactions are catalyzed by the same types of enzymes. Just as in other parts of the body, chemical energy is stored as ATP, and ATP is broken down to provide energy required for metabolism of mechanical function. A close correlation exists between the brain and other organs, especially the liver.2 Some compounds required for normal metabolism in the brain cannot he synthesized there and must be carried to the brain by the blood stream; others are removed from the brain and are metabolized and inactivated by different organs. Thus, neurochemistry does not concern itself solely with the metabolism of the nervous system proper hut also deals with other organs which are involved in the metabolism of com~ouudsrelated to the nervous system. In the May issue of THIS JOURNAL we shall develop some of the chemistry of the brain and nervous system in considerable detail. 1 NEEn~haa,. I . , "Frederick Gowland Hopkins," Persp. Bid. Med., 6 , 2 4 6 (1962). 'GEIGER,A,, "Correlation of Brain Metabolism and Function by Use of a Brain Perfmion Method in Situ," Physiol. Reu., 38, 1-20 (1958).
