Hudson Hoagland

The effect of ethanol ingestion on serotonin-C14 metabolism in man.

Abstract Low doses of ethanol ingested prior to serotonin-C 14 in man significantly decreased formation of urinary 5-HIAA-C 14 . The decreased formation of 5-HIAA-C 14 was dependent upon the dose and time of administration of ethanol and was related to the blood alcohol level. It was suggested that ethanol increased NADH and decreased NAD such that 5-hydroxyindoleacetaldehyde-C 14 derived from the serotonin-C 14 was preferentially converted to 5-hydroxytryptophol-C 14 with a concomitant decrease in 5-HIAA-C 14 .

A review of biochemical changes induced in vivo by lysergic acid diethylamide and similar drugs.

Studies of the physiological and biochemical factors associated with the socalled functional psychoses such as schizophrenia are surrounded by special difficulties. Perhaps the foremost of these is the fact that while what appears to be neurotic behavior can be produced in experimental animals, psychoses per se have not been satisfactorily demonstrated, and investigations have been limited, for the most part, to human beings. Most psychotics available for study are patients in state hospitals where, except for a few institutions that are notable exceptions to the rule, custodial care is routinized, and experiments with patients are discouraged. The patients in state hospitals are wards of the respective states, and the massive weight of bureaucracy is not conducive to the fluidity of attack and the imaginative approach necessary for effective research. Because of social attitudes toward mental patients and the isolation of much of psychiatry from the main stream of the biological and medical sciences, funds for physiological and biochemical research in the various aspects of mental disorders have been small. These limitations have resulted in meager advances in knowledge of neurophysiological and biochemical events underlying the disturbances of higher mental processes, and basic research in this field has been to date of little help to the practicing psychiatrist. Partly as a result of these limitations and partly as a consequence of the impact of the psychodynamic schools of thought with primary interest in psychotherapy, the basic investigations of the biology of schizophrenia have received scant encouragement either from psychiatrists or from the general public. Relatively few biochemists and physiologists have been attracted to the field in the past 2 or 3 decades. Quite recently this situation has changed as a result of the reawakened interest in psychopharmacology brought about by the psychotomimetic and tranquilizing drugs. This lack of interest in the biochemical approach has existed despite notable successes of various empirical advances in physiological therapies for mental patients, such as electroshock, metrazol, and insulin treatments, leukotomy and, more recently, the tranquilizing drugs. Very impressive, too, have been studies leading to the virtual eradication of 2 forms of major psychoses that were prominent in the past. Advances in syphilology have virtually eliminated general paresis, a psychosis often difficult to distinguish from schizophrenia by purely psychiatric criteria. The psychosis of pellagra, so prevalent in the southern part of the United States a generation ago, has also been relieved by correcting a chemical lesion due to a coenzyme deficiency. Both of these disorders were once regarded as “functional” in nature before their physical bases were understood. Today schizophrenia is regarded as a “functional psychosis,” in contrast to an “organic psychosis,” implying to many that i t involves no molecular lesion, but is a result of psychological experiences subject to correction by

A HUMAN PLASMA FACTOR INDUCING BEHAVIORAL AND ELECTROPHYSIOLOGICAL CHANGES IN ANIMALS: II. CHANGES INDUCED IN ANIMALS *

The historical background and methods of preparation of biologically active plasma and serum protein extracts, including the procedure currently used to prepare the extracts used in our laboratory, have been presented in the previous paper. We wish now to discuss the biological effect produced by these substances in animals. Blood samples were supplied by acutely ill psychotics within three days after hospitalization and before diagnosis has been established or drug therapy begun, or from chronic schizophrenics not on drug therapy. Usually two psychotics and one nonpsychotic subject were bled a t the same time into ion exchange blood packs (Fenwal). After separation of the cells a t the Protein Foundation Laboratories, Jamaica Plain, Mass., simultaneous processing of the three plasmas was performed by the aforementioned techniques. Using the Winter and Flataker rat climbing test‘ estimates of biological activity were made on samples equivalent to 5 ml. of original plasma injected intraperitoneally into 5 rats each unless otherwise stated. Values for the degree of impairment of climbing ability are listed as climbing-time delay CTD in units termed minute-seconds. Statistical significance of the results was evaluated by an analysis of variance. In our initial experiments we examined the effect produced in trained rats by injections of serum and plasma from nonpsychotic subjects and schizophrenic patients (TABLE 1) . Each sample was injected into 3 to 5 rats depending on the amount available. The first experiment with serum showed no elevation in CTD produced by 1-ml. samples from 19 schizophrenic patients over effects produced by equivalent samples from nonpsychotic subjects. The mean change of the CTD value produced by the psychotics’ serum from the nonpsychotics’ serum was -5.0 mine-sec., an effect that is not significant. Repetition of this experiment a t a later date compared effects on rat CTD produced by sera from 13 schizophrenics with an equal number of nonpsychotics’ samples. No consistent differences between the 2 groups were observed. Plasma samples, however, produced effects which clearly differentiated between the two groups. Whole plasma samples were compared under conditions similar to those employed using serum samples. In this series, usually 2 schizophrenics’ and 1 nonpsychotic’s plasma were tested simultaneously. Injections of plasma from schizophrenics increased the climbing time delay scores of the rats more than 100 per cent over the delay produced by the plasma from the non-psychotic persons. This difference is highly significant (p = <0.001). * The work described in this study was supported in part by Grant MY-2967 of the National Institutes of Health, Public Health Service, Bethesda, Md., by the Ford Foundation, New York, N.Y., and by the Scottish Rite Fund for Dementia Praecox Research, through the National Association for Mental Health, New York, N.Y.

Cybernetics of Population Control

This is the second in a series of articles dealing with developments in the life sciences of major importance for society. In the January issue, Dr. H. J. Muller discussed the “perspectives for the life sciences,” including the possibility of affecting human genetic heritage. Here, Dr. Hudson Hoagland, concerned with the world population explosion, describes mechanisms by which nature deals with overcrowding in animal species. That, similarly, there are natural mechanisms that could control the human population explosion is certain, but mankind should be able to use other methods, made possible by its higher intellectual and organizational status as compared to rats, lemmings, and rabbits.

Mans responsibility to his future.

The introduction to a symposium on genetic engineering discusses tha t man is the only animal that has or will have the knowledge to direct and control his own biological evolution through modification of the DNA structure. The significance of this ability in terms of law medicine ethics and human values is the subject of this symposium.

WHY FERTILITY CONTROL

Continuation of the present rate of population growth is a threat to all mankind. The application of techniques of modern medicine and public health since World War 11 to underdeveloped countries has markedly reduced death rates, leaving birth rates, always large, either unchanged or increased as the result of improvements in health and longevity. In many of these developing countries, increases of 20 years in life expectancy have occurred in the course of one or two decades-increases that took roughly a century to bring about in the United States and in western European countries. Population growth today depends only on the difference between birth rates and death rates, because there are no more vacant lands for colonization by people from crowded countries. World population today stands at some 3.6 billion and will double in 35 years at its current growth rate of two percent, so that by the turn of the century we will have some 7 billion people on earth, and in an additional 35 years, at our present growth rate, there will be 14 billion of us. Thus, a child born today and living on into his 70s would know a world of this number of people, and his grandson would live to see 60 billion people. Even the most optimistic can hardly think that our planet can support such a burden of humanity. Most concern with the population explosion has been expressed for the underdeveloped countries, which are being held back by the production of excessive numbers of children who are consumers, but not producers, who grow up hungry, and often with less education and job opportunities than were available to their parents. Capital for industrialization, for agricultural machinery, and for fertilizer plants is very hard to get, because produce for exports to obtain capital must be consumed locally. Competent economists and demographers predict mass starvation on a scale hitherto undreamed of in countries of Asia, Africa, and the Near East in from ten to 20 years. The so-called green revolution, the production of improved rice and wheat crops, is no answer. At best it can fend off the day of reckoning by only a decade or two. But, quite aside from food, there are other very serious considerations, because direct correlations have been made between occurrence of wars and revolutions, poverty, and rates of population growth, so that the likelihood of drastic population reductions by a third World War, with nuclear, chemical, and biological weapons, is increasing as human misery expands with numbers of hungry, ignorant, and frustrated people. Studies of animal societies have demonstrated conclusively the pathology of crowded living-f “pathological togetherness,” as John Calhoun has called it. Animal societies are organized in terms of dominance hierarchies, and their structure makes possible effective social living with a high biological survival value. Under crowded conditions, even with ample food, the social systems of gregarious animals collapse because of the stress of crowding, which operates

Technology, Adaptation, and Evolution

It is sometimes said that to end war, so deeply rooted in our biological aggressions, is contrary to human-nature. But flexibility of behavior and reason are mans outstanding traits, and love and cooperation are also deeply rooted biologically. It was thought by the best minds of the times that acts of depravity-slavery, human sacrifice, cannibalism, etc.—were necessities of human nature, but all have been abolished. War, which is a human institution, not characteristic of most aggressive animals, can also be abolished. Hudson Hoagland is President of the Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts; the following is a shortened version of a talk given by Dr. Hoagland before a meeting of the Society for Biological Psychiatry.