Popular Science Monthly/Volume 50/March 1897/Experiments on the Physiology of Alcohol I
THE following is Dr. J. S. Billings's statement on behalf of the committee: "This paper contains an account of some research work which has been done for the Committee of Fifty for the Investigation of the Liquor Problem, and it is to be regarded as merely a preliminary report to be considered in the final conclusions which may be reached in the future by the Committee of Fifty itself."
On my own part I desire to express to the Committee of Fifty my deep sense of appreciation for the support which has made the following researches possible. To the members of the Subcommittee on Physiology, Drs. Bowditch, Billings, Chittenden, and Welch, my especial thanks are due for hearty and sustained interest and prompt assistance at every turn of the investigation. Under their stimulus and guidance it has been throughout the keenest pleasure to work, even upon a problem so beset with prejudices that the slightest contamination of the atmosphere of pure science, in which such work, if ever effectual, must be done, would have rendered even the will to undertake it impossible.
The general point of view may be indicated in a few words. For centuries opinion has been divided on the subject, and the human experiment has been repeated, generation after generation, by individuals and on a national scale. But man is the most highly complex, most variable, most adaptable of animals, and the human problem has proved itself too complicated for scientific interpretation. Some men fail with alcohol, others fail as completely without it, and the same is true of success. Even "statistics relating to inebriety are too confusing," we find admitted in the Quarterly Journal of Inebriety.
Some may contend that the alcohol problem does not depend upon the science of physiology for its solution; but rather upon the moral, religious, or political functions of society. It should be remembered, however, that physiology is a broad science, whose ultimate aim is no less than to discover the laws and conditions under which may be developed the highest possible typo of man. By the intimate correlations between body and mind, and under the recent outgrowths of the mother science into modern psychology and neurology, physiology would cover the whole man, body, mind, and soul. And it would have not only a healthy soul and a sound mind in a sound body, but the most perfect soul, mind, and body which can be developed under physical conditions. Thus problems touching human welfare, even questions of ethics and social science, must ever draw important factors for their solutions from this science which is fundamental to the conditions and processes of life itself.
Extreme difficulty in solving such complicated equations is in part accountable for our lack of definite knowledge. But even this, it seems to me, does not constitute the most serious hindrance to the progress of science. In this country our greatest obstacle consists in a deficient notion as to what constitutes a scientific answer to a question. We are far too prone to say we "know" a thing is "true," when we lack sufficient evidence to convince an unprejudiced person of the fact. We mean simply that we "think," or we "guess," or we have a strong "prejudice" that such and such is the fact. Affirmation and prejudice are promptly met by contra-affirmation and prejudice, and with people who are satisfied with this sort of procedure scientific advance is at a standstill. We are too slow to realize that all progress in knowledge depends upon accumulation of wholly impartial evidence. Lacking this, no amount of legislating and voting and vociferating, can lay a smallest gravel corn of truth in the roadbed of human progress. As Bacon said so long ago, concerning the man who loses sight of this distinction and clothes his own beliefs with the reality of fact, "He shall exchange things for words, reason for insanity, the world for a fable, and shall be unable to interpret."
To meet difficulties connected with the intricacies and complexities of the problem, the method of physiology is clearly to reduce the equations to their simplest possible terms. By studying the physiology of alcohol in a number of simpler organisms, sufficient light may be thrown on the human experiment to render its interpretation possible. A unicellular organism is millions times less complicated than a human body; still, fundamental activities, nutrition, excretion, growth, reproduction, appear similar in both. So, too, the lower animals are proportionally simpler and also approach man physiologically more closely for purposes of comparison. Their conditions of life, too, can be made far more nearly comparable than it would be possible to either find or procure with men. With man, even after death, the microscopical study of the tissues to demonstrate the influence of alcohol upon them is so complicated by conditions of disease and post-mortem changes that no wholly trustworthy evidence is obtainable. On the other hand, animals may be killed in known conditions of health, and their tissues immediately prepared for examination; and in this way results have already been obtained by Berkley, Dehio, Stewart, and others, which have materially assisted in the interpretation of uncertain findings in human material.
Such a series of experiments should clearly be made on a number of different organisms, both plants and animals, in order that our basis for comparison and judgment may be sufficiently broad to enable us to distinguish between the constant and general effects of alcohol from those which are accidental or exceptional. And observations should be continued long enough to bring out clearly any more remote effects, especially those relating to heredity, of great importance, and about which much has been said but practically nothing is known.
It is intended in the following to outline the results of three series of experiments. Although necessarily incomplete in many ways, they may serve to demonstrate methods of research, and to show some of the possibilities of further work.
I. Experiments upon the Growth of Yeast. — The yeast plant, when sown in a nutrient solution, discloses an almost incredible power of growth and reproduction. This growth is wholly controlled by external conditions and by the composition of the nutrient medium. Probably no form of life approaches in power of rapid reproduction these minutest plants, the bacteria and yeasts, and none are probably more delicately responsive to varying conditions of life.
Yeast is able to grow until, by decomposition of sugar, its medium comes to contain fourteen per cent of common alcohol. At this point, no matter how much sugar and other nutriment remains, further growth is impossible.
Now, of especial interest to the physiology of nutrition, and the influence upon it of waste products generally, is the question,
What effect have very minute quantities of alcohol on the growth of yeast?
Fig. 1 represents to the eye, in the diagram to the left, the four possible kinds of action in the four lines diverging from the point marked "per cent." If no slowing effect is present until the poison limit, fourteen per cent, is reached, the line marked "normal" should be continued out until directly over a point corresponding to fourteen per cent strength of solution, and then should drop perpendicularly to the zero point of growth on the base line. As a matter of fact, Flügge states that growth is slowed with twelve per cent and stopped at fourteen per cent. If this be true, instead of dropping vertically, it would fall a little obliquely from twelve per cent to fourteen per cent. This would mean that up to a very high limit of concentration alcohol is absolutely harmless, that at a certain point it becomes suddenly toxic, and that slight increase beyond this concentration worked very rapidly to bring growth to a standstill.
A second possibility would be represented by a straight line, "Z," dotted line, falling uniformly from zero per cent to fourteen
per cent. This would indicate that the effect of the presence of alcohol in the culture medium upon yeast growth was a purely mechanical effect, a matter of friction, a clogging of the molecules, as it were. This would signify, the less alcohol the better, but that a small quantity has a comparatively slight effect, and that probably no harm is done in the way of changing the chemical reactions concerned in the growth processes of the yeast plant.
A third possibility, represented by dotted line "Y" in the figure, is in line with an idea not infrequently carried into practice, viz., that a little alcohol increases, "stimulates," activity, a larger quantity interferes with it. If this were found to be the case, the important matter to determine would be at what point of concentration alcohol ceases to be beneficial.
The heavy line, "M," represents the fourth possibility, viz., that minute amounts of alcohol have relatively a much greater retarding effect upon the growth of yeast than larger amounts. The line is plotted from the results of a series of experiments, of which a different expression is given in the diagram to the right in the figure. One thousandth of one per cent is seen to cause a considerable retardation of growth, over half as much as ten times the amount in one hundredth of one per cent, and about one fifth as much as the retardation caused by one hundred times as much alcohol, one tenth of one per cent. That is to say, we find a truly physiological curve, of practically the same form as that obtained from the fatigue of a muscle fiber or a nerve cell. This is not so remarkable, since in all such experiments we are touching, in final analysis, the vital activities of living cells, and in muscle or nerve one of the prime factors in causation of fatigue is accumulation of the waste products of active metabolism.
In the right-hand diagram in Fig. 1 and in Fig. 2 the same fact is expressed as a race — a competitive effort — in which the culture containing no alcohol is seen to win, the others falling behind. In general, retardation of growth is directly proportional to amount of alcohol. This is the unmistakable result of the entire series of experiments, fifteen in number. In Fig. 2, however, it may be noted that the cultures containing one per cent have grown somewhat better than those of 0·1 and 0·01 per cent. This is clearly due to difficulties in uniformly "seeding" the cultures, and when these were overcome perfectly consistent results, as seen in Fig. 1, were obtained.
Too great caution can not be used in interpreting the above results. While the physiology of the yeast cell and that of the cells of the human body may be at ground similar, in certain particulars they may be widely different. The yeast cell has not the power to oxidize alcohol. The cells of the body, or some of them at least, are most certainly able to bring about this reaction. Furthermore, if we had experimented with Mycoderma aceti — the normal food of which alcohol seems to be — we should have doubtless obtained a diametrically opposite result.
On the other hand, ethyl alcohol is found in minute quantities in the fresh tissues of man and animals where no alcohol has been given as a constant normal constituent. It has been distilled off from the brain, muscle, and liver. Whether it exists as a food in process of transformation or as a waste product, as in case of the yeast cell; whether it is a waste product from the activity of some cells and a food for others, it is impossible to say. While these questions remain open, it might be safe to assume, that if a food, the tissues are possibly, in conditions of health, able to produce all they need of it. If it is mainly a waste product, they should not be burdened with any more of it than necessary.
II. Experiments upon Kittens were broken in upon and complicated by accidents and disease to such an extent that we shall pass them by with a brief mention.
During April of 1895 four kittens were obtained, the two males, which we will call 1 and 2, from the same litter; the two
females, 3 and 4, from an unrelated litter. The males were born April 2d; the females, March 18th.
From April 23d to 29th they were weighed daily and studied as to health, liveliness, and general comparability. All four purred and played normally, but it was evident that 1 and 3 were considerably more vigorous and active. Both 2 and 4 had sore eyes — a rather serious indication of poor nutrition. Nevertheless, these were the most nearly comparable two pairs of kittens available at the time. Some doubts were entertained, but it was thought possible to bring 2 and 4 up to a comparable health level. Accordingly, allowing this much handicap to alcohol, it was decided to take the vigorous pair (1 and 3) for alcohol, and keep 2 and 4 for normal controls.
Alcohol, chemically pure, was now given, beginning with a dose of 1·3 gramme per kilogramme of body weight April 29th.
This dose caused scarcely appreciable intoxication, and was accordingly increased. At about two grammes per kilogramme light intoxication with tendency to drowsiness became manifest. The dose was still further increased until May 7th to 9th, when it had reached 3·6 grammes per kilogramme. This produced characteristic symptoms of intoxication — restlessness, incoördination of muscles, which began with weakness and paralysis of the hind legs and worked forward. Sleep followed in from twenty to twenty-five minutes, and lasted from two to three hours. It was deep and quiet, but both kittens could be awakened without difficulty.
During this time both purring and playfulness had been rapidly disappearing from the lives of the alcoholic kittens, and by May 9th both had become obliterated, and both kittens were pictures of demure and forlorn sadness. May 10th the alcoholics had severe colds, with discharge of mucus from the eyes and nose. Alcohol was discontinued until recovery could be effected, but this proved impossible. Severe catarrh of the nasal passages with conjunctivitis set in, the catarrh proving incurable and becoming chronic.
The chief value of the experiment thus far is to be found in the possession of control normal animals. None of these had been
similarly affected. In fact, both 2 and 4 had improved greatly under good treatment and healthful conditions. It seems thus safe to conclude that alcohol, as administered, caused a sudden and general breakdown in the two kittens; but, while seen thus clearly as a cause at the beginning, there is no way of determining how long it continued to act. Hence, from this point on, the experiment becomes mainly a history of disease. Practically it is an equation in which we do not know whether there are one or two unknown quantities, hence absolutely unamenable to solution.
In Fig. 3 is graphically expressed the relations of growth for the four kittens above described, and also for several other normal kittens of about the same ages that I happened to have at the time. It is seen that the alcoholic-diseased animals are dwarfed in growth to sixty-three per cent and thirty-nine per cent respectively as compared with their normal controls (see also Fig. 4). Some might be inclined to find in this evidence of the "stunting" influence of alcohol when given to growing animals which Bevan Lewis alludes to as "a well-known fact." This I was
|Fig. 5. — Alcohol-diseased kittens, 1 and 3, June 4, 1895: characteristic attitude. When the photograph was taken, 5 p. m., all the normal kittens were playing actively.|
strongly inclined to do at first, but we are not warranted in doing so from the evidence in hand. In the autumn one of my normal kittens (not one of the four) contracted catarrh, and her growth was interrupted for a time in a similar way. Hence we are obliged to leave this important point entirely in abeyance for the present.
On the side of their psychological development the falling out of purring and play are matters of the most serious import. Soon after beginning alcohol my notes abound in such expressions as the following: "1 and 3 dosing, 2, 4, 0 (another kitten), all playing actively" (see Fig. 5). Along with this all the instincts characteristic of healthy kittens, care of coat, cleanliness, etc., were almost wholly annulled. Fear of dogs, hunting and game instincts, were completely lost. This psychic collapse, developing so suddenly as it did, would seem to be directly attributable to the influence of alcohol. At any rate, nothing of the sort approaching it in either kind or degree was manifested in the normal kittens during any of their periods of disease. It will be wise to bear these points in mind until further confirmation and further analysis of the experiment with kittens are possible. Among the animals thus far experimented with the cat seems to be by far the most sensitive to the influence of alcohol.
From subsequent details of the experiment, a highly sensational story might be manufactured, but that could have absolutely no scientific value. We must eschew all such temptations, and never allow the thought to be dimmed that Science has a mission to perform in the world as great as the universe and as sacred as truth. She is in duty bound to yield all benefits of doubt; and she commits moral and intellectual suicide, falling to the level of the common "insanity" described by Lord Bacon, when she insists upon a single iota not supported by "evidence."
[To be continued.]
- Kinney, C. Spencer, M.D. The Quarterly Journal of Inebriety, 1896, p. 223.
- Berkley, H. J. The Effects of Alcohol on the Central Nervous System. Quarterly Journal of Inebriety, 1896, p. 109.
- Ibid. Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell. I. Alcohol. Brain, 1895, p. 473.
- Dehio, H. Centralblatt für Nervenheilkunde und Psychiatrie, 1895.
- Steward, C.C. Journal of Experimental Medicine, 1896.
- Flügge, C. Die Mikroorganismen. Leipsic, 1886, p. 482.
- S. cerevisiœ, obtained in pure culture from Fleischmann's compressed yeast, was used throughout these experiments. The chief difficulty encountered consisted in breaking up the large clusters, composed of hundreds of torulæ, so as to get a uniform seeding suspension. This was finally done by churning the culture from which it was desired to seed with a wad of sterilized absorbent cotton. The liquid squeezed out of the cotton contained only single torulæ. The seeding was always done from fresh stock solution — i, e., it was free from alcohol.
- Rajewski. Pflüger's Archiv, Bd. ii, S. 122. Hoppe-Seyler. Handbuch der chermischen Analyse, Berlin, 1893, S. 40 and 41.
- Given by their respective owners with full knowledge as to the experiment to which they were to be submitted.
- Tested by evaporation at room temperature.
- It was first attempted to have the kittens take the alcohol mixed with warm milk. On their refusal to be thus imposed upon, it was given, diluted to twenty and thirty per cent, by stomach pump, always after meals, the normals being given an equal amount of water in the same manner.
- W. Bevan Lewis. A Text-Book of Mental Diseases. London, 1889, p. 306.