Popular Science Monthly/Volume 59/May 1901/Recent Physiology

By Professor G. N. STEWART.

EVERY year a mass of original work in physiology, covering from ten to fifteen thousand pages, for the most part of formidable size and closeness of print, is collected in the various special journals of the science, or mingled with kindred, though miscellaneous, dust in the transactions of learned societies, or decently buried at the public expense in government bulletins and official reports. Those four hundred square yards of printed matter embrace, on the average, more than five hundred papers in German, English, French and Italian, without reckoning stray messages in less familiar tongues, such as Russian, Polish, Dutch, Spanish, the Scandinavian languages, the dog Latin of graduation theses, and even, it may be Japanese, Arabic and modern Greek. The great majority of these communications either contain new facts or are directed, often with notable acuteness, to the unfolding of new relations between facts previously established. It is obvious that no survey of recent physiology which is possible within the space at our disposal could pretend to exhaust the contents of its crowded archives even for a single year. I shall try rather to trace the main tendencies, while incidentally mentioning some of the outstanding achievements of recent physiological discussion and research, than to enter in any detail into the results of particular investigations. Foremost among these tendencies is the study of the structure and functions, and especially the chemical and physico-chemical relations of the individual cell, in which, as has been well said by Bunge, in his brilliant Lectures on Physiological Chemistry, lies ever the riddle of life. While the mode of action of the complex physiological mechanisms, built up by the grouping and chaining together of cells of the same or of different kinds, deserves and has attracted the most assiduous attention, it has become more and more apparent that, as we push our enquiries back, we are always, sooner or later, arrested at the boundary of the cell. We attempt, for example, to explain the mechanism by which the circulation of the blood is maintained and regulated, and up to a certain point we succeed tolerably well. We recognize as the central factor the rhythmically contracting heart which forces the blood through the branching arteries into the netted labyrinth of the capillaries, whence it is again conveyed to the heart by the veins, and thus completes its destined round. We know that the rate and force of the heart-beat and the caliber of the blood vessels are controlled by efferent nerves carrying impulses down to them from centers situated in the medulla oblongata, the portion of the central nervous system that serves to join the spinal cord to the brain. We are further aware that those centers are in touch with all parts of the body by afferent nerves, along which impulses are continually streaming to the centers. It is thoroughly established that the activity with which the centers discharge impulses along the efferent nerves to the heart and the vessels is modified by the arrival of afferent impulses. And it is fairly well understood how, by the action of this craftily balanced apparatus of nerve-fibers and nerve-centers, the supply of blood to the various tissues is adjusted to their ever-changing needs. But when we ask ourselves what happens in one of the nerve-cells which compose the nervous centers when it discharges an impulse? what that impulse which flies at the rate of a hundred miles an hour along the nerve-fiber really is? what is the precise nature of the actions which it arouses or represses in the muscular fibers of the heart or of the arteries when, in the twinkling of an eye, it impinges upon them? we have to answer that we do not know. We are in exactly the same position with regard to the voluntary contraction of the striped or skeletal muscles by means of which the ordinary movements of the body are executed. The nerve cells in which the impulses originate have been located with considerable precision in the so-called motor region of the brain, which comprises the middle portion of the superficial gray matter of each hemisphere. The tracts of nerve-fibers along which those impulses pass to the muscles have been mapped out. The influence of temperature, tension and other conditions on the muscular contraction has been investigated in great detail. But we are again almost completely in the dark as to the actual nature and course of the events that take place within the envelopes of the nerve-cell, the nerve-fiber and the muscular fiber when a muscle contracts in obedience to the will.

One or two promising clues there are, and these are being vigorously followed. Whenever a nerve or a muscle (or, indeed, for that part, a gland, although the phenomena are best seen in muscle and nerve) enters into a condition of physiological activity, an electrical change is set up in the excited part. In muscle, although not as yet in nerve, certain chemical, thermal and optical changes can also be demonstrated. It is obvious that the study of such phenomena, and especially their quantitative study, under as many different conditions as possible, is essential to the solution of our problem. Accordingly, data of this kind, which, it may be hoped, will some day become the basis of a great generalization, are being diligently gathered. Among the most important of recent contributions to the subject is an elaborate investigation of the electrical changes which accompany muscular contraction by Sir John Burdon Sanderson. By photographing the movements of the mercury in a capillary electrometer connected with the muscle he has obtained a great series of marvelously beautiful records. Gotch and his pupils, using a similar arrangement, have been able to record the electrical changes in active nerves, even when stimulated by rapidly recurring shocks from an induction coil. It may surprise those who have not followed the progress of technique in the biological sciences to learn the extent to which photography is now applied in physiological research. Pictures of even such feeble vibrations as those which give rise to the sounds of the heart may be obtained by connecting a microphone placed near the chest and the primary coil of an induction machine in the same circuit, and photographing the movements of a capillary electrometer connected with the secondary. Exquisite photographs of the electrical variations occurring in the human heart at each beat, first demonstrated by Waller, have been recently published by Einthoven and Lint.

Loeb, working from another direction, has studied the effect of the ions contained in solutions of certain simple salts on rhythmical contraction in general, and particularly on the rhythmical contraction of the heart. He starts with the observation that a striped muscle in a solution of sodium chloride of a certain strength carries out rhythmical contractions which may last 24 to 48 hours. Salts of lime and of potassium hinder the contractions. Nevertheless the muscle remains longer alive when a small amount of calcium or potassium chloride is added to the sodium chloride solution. He explains the seeming paradox by the hypothesis that the sodium ions are the real stimulus for the rhythmical contractions, but yet exert on the muscle a poisonous influence, which, is counteracted by the calcium and potassium ions. He finds support for the idea that the sodium ions are actually poisonous to the living substance in the fact that Fundulus heteroclitus—a small marine fish with so marvelous a range of adaptation to its environment that it will live, on the one hand, in sea-water to which sodium chloride has been added to the amount of five per cent., and, on the other hand, in fresh and even in distilled water—-wall not live in pure sodium chloride solutions of about the same strength as sea-water, but will survive in sodium chloride solutions even twice as strong if a little chloride of calcium or of potassium be added. According to Lingle, one of the pupils of Loeb, sodium ions, while acting as the normal stimulus to the discharge ©f rhythmical contractions by the heart muscle of the turtle, exert upon it, in the absence of calcium and potassium ions, the same deleterious influence as upon striped muscle, a fact also demonstrated by Ringer and others for the heart of the frog. These are the experiments which that eminent contributor to the gayety of nations, the scientific newspaper reporter, has recently travestied under the caption, 'Discovery of the Elixir of Life in Chicago.' They have yielded fresh evidence that the differences between muscular fibers, such as those of the heart, which contract normally with what we call a spontaneous beat, and the fibers of the skeletal muscles, which only, under ordinary circumstances, contract when excited through their motor nerves, are not so deep-seated as was at one time supposed, since the addition of simple inorganic bodies to the living muscular substance, or their subtraction from it, can alter its behavior in this regard. The experiments of Langendorff, Porter and others on the action of the isolated hearts of warm-blooded animals, which, after being cut out of the body, can be kept alive for several hours by feeding them through their arteries with warm blood from a reservoir, have strengthened the belief that the essential cause of the heart-beat is to be sought in the muscular fibers and not in the nerve-cells present in certain portions of the organ.

With respect to the nerve-cell, research is at present largely concentrated upon the study of its minute structure. Among the numerous methods of staining employed for this purpose two deserve especial mention: the method of Golgi, which is peculiarly useful for bringing out the processes or branches of nerve-cells, and the method of Nissl, which is of great service in the investigation of the body of the cell. A typical nerve-cell when impregnated with a salt of silver, according to Golgi's method, exhibits a wonderful profusion of bifurcating processes, picked out in black like the sharply shadowed branches of a leafless tree under an electric light. But, however intricately the branches of neighboring cells may mingle and intertwine, they do not in general run into, or fuse with, each other, any more than the interlocking boughs of neighboring trees in a forest. By demonstrating this important fact the method of Golgi has revolutionized our ideas of the architecture of the nervous system.

The significance of the peculiar angular or spindle-shaped bodies in the protoplasm of the nerve-cell, which have been revealed by Nissl's method of staining with methylene-blue, is at present arousing the greatest interest. That they have some important relation to the nutrition of the cell seems evident. For when the latter is severed from that one of its processes (the axone) which constitutes the essential part of the nerve-fiber that springs from the cell, the Nissl bodies break up, and either disappear or are dispersed in the form of very minute granules of stainable material in the protoplasm. At the same time the cell becomes swollen, its nucleus is displaced to one side, and it may even atrophy entirely and disappear. As a rule, however, after several months it recovers its normal structure. The administration of considerable quantities of alcohol and other drugs causes a similar effect on the Nissl bodies. It has been known for half a century that the axone degenerates when cut off from the cell of which it is a process. The fact that the cell suffers also is a striking illustration of the essential unity of the nerve-cell and all its branches, whether they are long or short—three feet in length, as the axones that run from the lower part of the spinal cord to the foot may be, or a thousandth of an inch, like some which arise and terminate within the gray matter of the cord and brain.

Simpler, at first sight, in their action and organization than nerve-cells or muscular fibers are the gland-cells which secrete the digestive juices. The cells of the kidney which separate from the blood the constituents of the urine, and the cells which line the intestine and are engaged in the absorption of the food appear to be simpler still. And simplest of all are the flat, scale-like cells that line the lungs and have to do with the taking in of oxygen and the elimination of carbonic acid and the similar cells which form the walls of the capillaries and are concerned in the production of lymph. Accordingly we have seen of late years, in connection with researches on the functions of such cells, a revival of formal discussion of the general problem of physiology: whether the vital processes can be completely explained in terms of the laws of unorganized matter. This is a question which has had a singular fate. Answered at certain epochs by an almost unanimous negative, it has emerged again with every fresh advance in mechanical, physical or chemical knowledge, and for a time has seemed about to be settled in the affirmative. It was so in the seventeenth century when the discoveries of the new geometry and the new mechanics were hailed by Descartes and the iatro-mathematical school who were his lineal descendants, although they denied their parentage, as the key which was to unlock all the secrets of that cunningly devised automaton, the animal body, and particularly to explain its movements. At a later date, the determination of the laws of the diffusion of gases appeared to solve the problem of the passage of gases through the lungs, and the determination of the laws of diffusion of dissolved substances and of endosmosis, the problem of absorption from the intestines. With Ludwig's researches on the formation of urine, secretion seemed about to pass out of the group of mysterious 'vital' phenomena, and to become a mere process of filtration. But always as renewed investigation has brought into clearer light the peculiarities, the wizard tricks, one might almost say, of those rare mechanisms that ply so deftly even in the common business of the bodily machine, the gulf that separates the inorganic from the organized world has opened wide as ever, and physiology has still had to wait for a new Curtius to close it.

Quite recently the experiments of de Vries, Van't Hoff and others on osmosis have supplied further physical data for the solution of this perennial problem, and have, therefore, become the starting point of numerous physiological researches. Among these may be mentioned a series of studies on absorption from the intestine by Waymouth Reid, which have just been published, in collected form, in the 'Philosophical Transactions of the Royal Society' Starting with the idea of studying the behavior of the intestinal wall when as many as possible of the physical factors which may be supposed to be concerned in absorption have been eliminated, he endeavored to realize this condition by introducing into the intestine of an animal some of its own blood-serum. When this is done the cells that line the alimentary tube are in contact on one side with blood-serum and on the other with capillary vessels containing blood, the liquid portion of which has the same composition as the serum in the intestine. Under these circumstances there could be no passage of material from the intestines to the blood by diffusion or osmosis, if the intestinal wall acted like an ordinary dead membrane. Reid found, as a matter of fact, that the serum was rapidly absorbed. That this was not due to ordinary filtration, that is, to the squeezing of the liquid through the walls of the tube, follows from the fact that in these observations the pressure in the intestines was less than in the capillaries. He comes to the conclusion that while known physical forces play a certain part in absorption, there remains an unexplained residuum. But he refuses to speculate as to the cause of the peculiar endowments of the intestinal epithelium, and is very careful to point out that what seems so inexplicable now may later on become susceptible of explanation.

Friedenthal, in a suggestive paper occupied mainly by a critique of previous work and contemporary speculation, has lately taken up his parable in favor of a complete physico-chemical explanation of absorption. According to him, what we call the selective power of the intestinal epithelium is simply the expression of the fact that there exist in those cells substances which have a greater affinity' for certain constituents of the intestinal contents than for others, just as plates of gelatine do not take up the same quantities of different salts and other compounds from solutions containing them. Such hypotheses, of course, while they have the merit of directing attention to the possibility of a complete chemical or physical solution of the problem being some day found, do not give us any information as to the peculiarities of physical structure or chemical composition which confer on the lining of the intestine, as on all living cells, powers so remarkable that when we endeavor to describe them the terms which spring spontaneously to our lips are such as we should apply to the behavior of an entire organism in relation to its environment: 'selection,' 'discrimination,' 'affinity' for substances that are useful, 'antagonism' to those which are injurious.

The study of the permeability to various substances of what we may perhaps consider as the most simply organized cells in the whole body, the colored corpuscles of the blood, promises to throw a flood of light on absorption in general. It has been lately shown that they are practically non-conductors of electricity in comparison with the liquid portion of the blood, or plasma, in which they float. This is due to the fact that the salts of the plasma, whose ions carry the electricity, penetrate the corpuscles with difficulty, sodium chloride, for example, scarcely passing into them at all. On the other hand, they are freely permeable to ammonium chloride, urea and other bodies. The conditions governing the passage of substances into the corpuscles are evidently very different from those which determine the permeability of an ordinary membrane. This is further shown by the fact that by certain methods of treatment the colossal molecules of the red coloring matter of the blood may be caused to escape from the corpuscles, while the much smaller molecules of the inorganic salts remain still pent within them. Such results are of great interest, for they show that cells which, as regards their main physiological office, the conveyance of oxygen to the tissues, seem to be governed strictly by the physical laws of diffusion of gases, appear to exercise a kind of 'selection' in the taking up of many substances which have nothing to do with their particular function. The suggestion is scarcely to be avoided that in this case a purely chemical or physical 'attraction' underlies the apparently selective power. And this idea is strengthened by the fact that all those characteristic reactions of the colored corpuscles can be obtained many hours after the blood has been removed from the body, and, therefore, at a time when their 'vital' activity may be supposed either to have been extinguished or to have undergone a serious diminution.

The absorption of oxygen and excretion of carbonic acid by the lungs have long been considered conspicuous examples of the passage of substances through a living animal membrane by ordinary physical diffusion. But, according to the recent observations of Bohr, oxygen may, within certain limits, be absorbed, when its partial pressure or tension in the blood is greater than that in the air contained in the lungs, and carbonic acid may be excreted when its pressure in the blood is less than that in the air of the lungs. Haldane and Smith have indeed shown that in man the pressure of the oxygen in the arterial blood is actually higher than in the outside air. These results are, of course, incompatible with a simple theory of diffusion, and show that the cells of the pulmonary membrane have the power of forcing oxygen to move in one direction and carbonic acid in the other even against the slope of pressure.

As regards the physiology of particular organs, attention has been, in recent years, attracted in a marked degree to two subjects: the so-called internal secretions of certain glands and the arrangement and actions of the nerve-cells and fibers which make up the central nervous system.

By an internal secretion we mean a substance or substances formed by a gland and taken up from it by the blood or lymph. An ordinary external secretion is discharged by a special duct into the proper receptacle, bile, for example, into the gall-bladder, and ultimately into the intestine; urine into the urinary bladder, and so on. Some of the glands which produce important internal secretions have no ducts. Such are the thyroid glands, two insignificant looking reddish bodies situated in the neck, one at each side of the windpipe, a little below the larynx. It had been long known that disease of these glands, commencing in childhood and leading to the enlargement which we call goitre, was often associated with a condition of idiocy (cretinism). Interest in their functions was greatly stimulated by the discovery that excision of the thyroids was followed by grave changes resembling those found in a disease called myxedema, and that the symptoms produced by excision, as well as those present in the natural disease, could be removed, and health restored, by feeding the patient with the raw or slightly cooked thyroids of animals or with certain extracts prepared from them. Much work has been devoted to the isolation in a pure form of the active substances, one of which contains iodine as an important constituent. It appears to be the office of the thyroid to manufacture for the use of the body a constant supply of these substances, which are necessary for the due maintenance of certain of its functions. In the absence of the natural supply, similar materials produced by the corresponding glands in animals can be utilized.

The suprarenal or adrenal bodies, situated just above the kidneys, are another pair of ductless glands whose function is of extraordinary importance in proportion to their size. It has been shown that they contain a substance which when injected into the blood in animals, or painted, say, on an inflamed eye in man, causes a marked narrowing of the small arteries; and it has been surmised that this substance, oozing slowly from the glands into the blood, exerts a bracing or 'tonic' influence on the muscular fibers of the heart and blood vessels, and helps to keep them in proper condition for their work. Certain it is that death follows their removal in animals, while their disorganization in man is associated with the peculiar and fatal condition termed Addison's disease.

The pituitary gland, a small body attached to the base of the brain, is in the same category. It seems to be of great importance, if not absolutely indispensable to life. Extracts of the gland, as Howell and Schäfer have shown, produce decided effects upon the pressure of the blood when injected into the vessels.

One of the most interesting examples of an internal secretion which is not necessary to life but which yet profoundly affects the chemical changes occurring in the body, is that of the ovaries. It has long been familiar to stock farmers that the removal of these organs greatly increases the rapidity with which fat is laid on. According to the recent researches of Loewy and Richter at the Agricultural College in Berlin, the explanation is that the ovaries produce a substance which hastens the oxidation of the tissues and the food. When this substance is injected below the skin of animals whose ovaries have been removed, the tissue waste is markedly increased.

In the domain of nervous physiology our knowledge is growing apace. The doctrine of the localization of function on the surface of the brain may now be considered as well established. The motor region has been subdivided into areas, each of which is related to a particular movement, because the nerve-fibers springing from the large pyramidal cells contained in it, are connected with nerve-cells in the gray matter of the spinal cord which send nerve-fibers only to the muscles concerned in that movement. But while each motor center is thus connected by motor or efferent fibers with the muscles, recent work by Sherrington and Mott and by other observers has shown that it is also connected by sensory or afferent fibers with the muscles, the skin overlying them, the joints in their neighborhood, and the bones which they move. The 'motor area,' in fact, is not purely motor, but has sensory functions as well.

No convincing proof has yet been given that any particular portion of the brain is exclusively concerned in intellectual operations. Goltz, the most prominent representative of the dwindling band who still refuse to believe in the localization even of the motor functions, has lately published an interesting paper containing the results of observations on a monkey which was carefully watched for eleven years after the removal of the greater part of the gray matter of the middle and anterior portions of the left hemisphere of the brain. The character of the animal, whose little tricks and peculiarities had been studied for months before the operation, was entirely unaffected. All its traits remained unaltered. On the other hand, disturbances of movement on the right side were very noticeable up to the time of its death. It learned again to use the right limbs, but there was always a certain clumsiness in their movements. In actions requiring only one hand, the right was never willingly employed, and it evidently cost the animal a great effort to use it. Before the operation it would give either the right or the left hand when asked for it. After the operation it always gave the left, till by a long course of training, in which fruit or lumps of sugar served as the rewards of virtue, it learned again to give the right. Evidently, although this is not the interpretation placed by Goltz upon his observations, the motor centers of the right side of the brain, which normally preside over the movements of the left side of the body, had to be laboriously educated before they became able to carry out such movements of the right hand.