General Physiology: An Outline of the Science of Life

While light, at least in its ordinary intensity, is, according to experiments thus far, not a general excitant of living substance, it is still less a depressant. The few depressing effects of light that have been reported must be received as such with great caution ; they have been little investigated and their suggested interpretation is extremely doubtful. The phenomenon, e.g., that the growth of plants in the light is less than in the dark might be regarded as a phenomenon of depression ; it might be imagined that light directly inhibits certain metabolic processes that are necessary to growth. But the growth of plants is a very complicated phenomenon, one in which many different factors play a role, and, as Sachs l has already emphasised, at present it is impossible to judge how far light as such has a share in its occurrence.

Another depressing effect of light might be sought in the influence of the latter upon the production of light by many luminousmarine animals. For example, the statement has oftenbeen made that pelagic animals, such as Ctenophora and Siphonophora, when brought from the light into the dark, do not emit light, and only after they have remained in the dark for some time can they be made by stimuli to do so, at first feebly and later more strongly. The power of producing light in these organisms appears, therefore, to be depressed by the influence of light, and since the unicellular Noctilucce are said to behave similarly, it should not be assumed that the phenomenon depends upon a secondary effect of light, mediated by the sense-organs and the central nervous system. But the matter is very uncertain, for, although the doubtful phenomenon has been observed by several persons, thus far it has never been investigated.

Little more is known of the depressing effects of light, and the question whether light is able to call out phenomena of depression at all must remain for the present undecided. In many respects the electrical stimulus stands in peculiar contrast to other stimuli. In nature it comes into contact with living organisms only in exceptional cases ; this is true also of many chemical stimuli but of no others. Nevertheless, it possesses many properties that make its employment upon living substance especially easy and convenient. It can be graded in intensity more conveniently than any other and with a fineness that answers the highest requirements. Further, its employment can be limited in time in any desired manner. These great advantages, which have

been put to their utmost practical use in the ingenious methods of electrical stimulation, are the reason why in the special physiology of the vertebrates, wherever the effects of stimulation of definite organs are studied, the electrical stimulus is employed almost exclusively. Of the various methods of producing electricity (friction, contact, induction), we employ for stimulating purposes in physiology exclusively the galvanic current, obtained by contact or induction, because this offers the greatest advantages by

reason of its constancy and certainty, its convenient handling and applicability, and the capability of its being finely graduated in intensity and duration. Since the methods of galvanic stimulation have developed to very great complication and delicacy, it will be advantageous briefly to consider some of the most important apparatus. As has been seen elsewhere,1 a galvanic tension arises when two strips of different metals or certain other bodies are dipped into a feebly acid liquid. A strip of copper and a strip of zinc, the lower ends of which dip into a vessel containing dilute sulphuric acid, while the upper ends project freely into the air, constitute the most primitive form of a galvanic element (Fig. 188) ; in it between the two free ends of the zinc and the copper a tension exists of such a kind that the end of the copper is electrically positive, the end of the zinc electrically negative. If the two ends be united by a metallic conductor, such as a wire, at the moment when the union is established, the electrical tension becomes equalised. Since, however, the tension is being constantly renewed at the place of contact of the metals with the liquid, there results a continuous equalisation, which is termed a constant galvanic current. The continuity of copper, wire, zinc, liquid, and copper, forms in a certain sense a closed circuit, in which the current flows. This galvanic current has always the same direction ; outside the liquid it flows from the copper, the positive pole, through the wire to the zinc, the negative pole. In the liquid its direction is evidently reversed ; from the zinc, through the liquid, back to the copper ; but this reversal need occasion no confusion, since it is customary to term the poles outside the liquid the positive and negative poles. The copper is the positive, the zinc the negative

FIG. 188.— Galvanic element. The free pole of the zinc (-) is joined to the free pole of the copper (+) by a wire ; a circuit is thus formed, in which the direction of the current is indicated by the arrows. pole, or, as it is also said in order to express in words the direction of the current, the copper ( + ) is the anode, the zinc ( — ) the kathode. This primitive form of galvanic element, upon which, slightly modified, is based the very powerful chromic acid dip-element in which carbon and zinc dip into dilute chromic acid, has proved for many purposes unserviceable. If the circuit be kept closed for a considerable time, i.e., if the metallic union between the two ends of the metals be not interrupted, or, as is said, the current be not " broken," it is found that the current is not so strong as at the beginning. This depends upon the fact that certain substances, the so-called polarisation-products, have become formed by electrolytic decomposition, have accumulated at the two ends of the metals within the liquid, and by contact with the liquid give rise themselves to a galvanic current, which is opposed to the original current and, therefore, gradually weakens it. In order to prevent the appearance of this polarisation-current and thus to maintain the intensity of the original current as constant as possible, the expedient has been employed of dipping the two metals into different liquids, which are separated from one another by a porous partition-wall of clay, and are so constituted that they destroy the efficiency of the polarisationproducts at the very moment of their appearance. Hence a polarisation-current cannot develop, and the electromotive force of the element remains constant. Such constant elements are in use in various forms. The best-known forms and those that are employed most in physiology are that of Daniell, in which zinc dips into dilute sulphuric acid, and copper into a concentrated solution of copper sulphate; that of Bunsen (Fig. 189). in which zinc dips into dilute sulphuric acid, and carbon into concentrated nitric acid ; and that of Grove, in which zinc dips into dilute sulphuric acid, and platinum into concentrated nitric acid. In all, the free zinc pole is the kathode.

These galvanic elements are sources of electricity ; from them at any moment a galvanic current can be led off very conveniently wherever desired. In order to stimulate galvanically a living object, e.g., a nerve-muscle preparation of a frog, it is necessary simply to cut the wire that joins the two metals of an element and insert the preparation between its ends; the current then FIG. 189. — Bunsen's element. The carbon plate (+) stands in a clay cylinder containing concentrated nitric acid. The cylindrical zinc plate (-) surrounds the clay cylinder, and stands in a vessel containing dilute sulphuric acid.

flows through the preparation (Fig. 190, /). But, in order to be able at any moment conveniently to interrupt the circuit and again to close it and thus to control arbitrarily the influence of the stimulus upon the preparation, there is inserted into one wire a so-called galvanic key, which consists of a cup set into a plate of insulating hard rubber and containing mercury into which one end of the wire dips, while the other is in metallic connection with a small lever ; at any moment the lever can be dipped into the mercury or withdrawn, so that the metallic conduction can be established and again interrupted, or, in other words, the current can be made and broken (Fig. 190, //).

When currents are allowed to act on the preparation for a considerable time the metallic wires themselves should not be FIG. 190.— 7, Circuit between the element E and the nerve N of a nerve-muscle preparation ; in the circuit is the key S. //, Mercury key. laid as electrodes on the nerve, the muscle or other tissue, since at the place of contact of the metal with the preparation, which latter is a moist conductor, opportunity would be given for the development of polarisation-currents, which would themselves stimulate the preparation and thus disturb the experiment. In order to avoid this, so-called non-polarisable 'electrodes have been constructed, which allow no polarisation-current to develop at the place of contact with the preparation.1 These non-polarisable electrodes consist in their most convenient form of a short glass tube, closed below by a stopper of plastic clay, into which a short soft camel's-hair brush projects ; the lumen of the tube is filled with a concentrated solution of zinc sulphate, into which dips a zinc rod connected with the conducting wire (Fig. 191). The electrodes are held in adjustable stands and can be handled with extreme ease, the pointed brushes being laid upon the preparation. After having become acquainted with a reliable source of

electricity in the galvanic element, it is necessary to graduate finely and in any way desired the intensity of the current. For this purpose we must consider somewhat fully the fundamental law which formulates the facts regarding the intensity of electricity. This is Ohm's law; it may be stated as follows: the strength of a current is directly proportional to the electromotive The electromotive force depends upon the kind and number of the elements. Many elements have only slight electromotive tension, others very high tension ; and if two or more elements be coupled together so that unlike poles are joined with one another, the current is considerably stronger than that afforded by a single element. According to Ohm's law, the chief means of strengthening or weakening the intensity / of a current consists in increasing or diminishing the number of the elements, for thereby the electromotive force E is increased or diminished. But this graduation by change of the electromotive force is very crude and does not allowT delicate changes to be made. Hence, where finer graduations are required, the second factor upon which, according to Ohm's law, the intensity depends, is employed,

namely, the resistances W. The resistances are of two kinds : on the one hand, internal resistance, that which exists in the element itself, especially in the liquid, which is a moist and, therefore, a bad conductor of electricity; on the other hand, external resistance, which exists outside the element in the kind, the length, and the diameter of the conductor. The latter especially can be graduated very delicately. Metals are good conductors, and for this reason metallic wires, and best copper wires, are always selected as conductors outside the element. Their resistance is less, the shorter the conduction and the greater their cross-section. A very ready means of increasing the

FIG. 191. — A non-polarisable electrode. A glass tube closed by a stopper of clay and filled with a concentrated solution of zinc sulphate is held in the movable stand. A moist camel's-hair brush sticks into the clay stopper, and a zinc rod, to which the wire is carried, dips into the solution. The nerve of the preparation is laid over the brushes of two such electrodes. resistance and thereby diminishing the intensity of the current by any desired amount is that of lengthening the conducting' wire and using wires that have a small cross-section.

Upon these facts is based a principle which comes into general use in apparatus that is employed for graduating the intensity of the current, viz., the principle of the accessory or short circuit. If, e.g., a circuit from an element E (Fig. 192, 1) extend through copper wires to a preparation N, a galvanic current of a definite intensity, which can easily be measured, flows through the preparation, although the latter as a moist conductor affords considerable resistance. But, if into this circuit a short circuit be introduced by joining two opposite points of the metallic conductor by means of a cross-wire, a small circuit is made to

FIG. 192.— Scheme of the short circuit. /, A simple circuit ; //, long circuit with short circuit. E, element ; N, nerve-muscle preparation ; A , B, short circuit. branch off from the large one ; in the former the resistance is considerably less than in the latter, since its conductors are metallic and shorter than those in the latter. The result is, as Ohm's law directly teaches, that in the long circuit a current of slight intensity passes, which is so feeble that under certain circumstances it has no effect whatever upon the preparation, while in the short circuit there is a current of considerable intensity. Hence in the long circuit, in which the preparation is, there are two extremes of intensity: with the short circuit broken, a considerable current, and with the short circuit closed, a very slight current. From the latter extreme to the former the intensity can be graduated very delicately by successively increasing the resistance in the accessory circuit, until it becomes so great that the circuit hardly conducts at all. Then nearly the whole current goes through the large circuit and the preparation.

Du Bois-Reymond employed the principle of the accessory circuit in his rheochord, an apparatus that serves to increase the intensity in the circuit of a preparation as desired, by shunting definitely measured resistances into an accessory circuit. For resistances fine wires of definite length are employed, which can be introduced one by one into the accessory circuit. The apparatus (Fig. 193) consists in its essential parts of a thick bar of brass, the continuity of which is broken at definite distances so that it is really a series of separate metal blocks, which, however, can be joined into a single bar by the introduction of metallic connecting pieces. Each of these brass blocks is joined to the adjacent block by a very thin conducting wire of a definite length, and upon the wire that joins the first two blocks a metallic slide can be shoved to and fro, so that the wire can be shortened or wholly cut out by shoving up the slide. This whole apparatus is inserted as an accessory circuit into the circuit of the preparation in such a way that the two wire poles lead from the source of the current to the brass bar, and from there two other wires lead to the preparation. If, now, all the connecting plugs of the metal blocks are inserted between the blocks, so that the brass bar is continuous, the condition that is represented in Fig. 192, // is obtained. A strong current passes through the short circuit, because there is little resistance there, while through the long circuit a very feeble current flows, because there the preparation affords considerable resistance. But the weak current going through the

circuit of the preparation can be strengthened very conveniently by increasing the resistances in the short circuit, and this is accomplished by shoving down the slide, farther and farther, so that the current must pass through a constantly greater stretch of the first wire of the rheochord, the distance being measured upon a scale. The resistances can be strengthened still more by removing one by one the connecting plugs between the metal blocks. The result is that finally the current in the short circuit must traverse all the wires of the rheochord, which with their fineness and length form a very considerable resistance. But the more the resistances.

increase in the short circuit, the more does the current that passes through the circuit of the preparation increase in intensity, and, since the resistances are measured exactly, the intensity of the latter current can be graduated very delicately. Finally, we must consider the methods of allowing a current of momentary duration to act upon the preparation, and of producing currents of momentary duration in rapid rhythmic succession. These are presented by the phenomena of induction.

If two coils of wire are in the same vicinity but not in contact with one another, and if a constant current be allowed to flow through one, the so-called primary coil (Fig. 194), at the moment of the making of this primary current there appears a current in the second, the secondary coil. This induced current is of very brief duration ; it exists at the moment of making the primary current, but disappears at once. So long as the primary current passes through the primary coil, not the slightest current is

FIG. 194.— Scheme of induced current. I, Primary coil ; £, element ; S, key. II, Secondary present in the secondary coil ; but a brief induced current appears again in the secondary coil as soon as the primary current is broken. Thus, an induced current appears only at the moments of making and breaking the primary current. The making induced current is, however, in certain respects essentially different from the breaking induced current. While the direction of the former is opposite to that of the primary current, the breaking induced current has the same direction as the latter. This fact is important, for it explains at the same time another difference between the making and breaking shocks. If the current in the primary coil be made, it induces at the time of its appearance not only in the secondary coil, but also in the turns of its own coil, a current in the opposite direction ; and this extra current running in opposition to it hinders the increase of the primary current, until the latter has reached its greatest intensity, when the induction-effect ceases. The case is different at the breaking of the primary current, for the extra current that then appears in the turns of the primary coil, has the same direction as the primary

current. Hence, an essential difference between the making and the breaking induction-shocks is observed in the secondary coil, since with the former, on account of the slow increase of the primary current, the electric tension is more gradually equalised than with the breaking shock, where the equalisation takes place very suddenly. If, therefore, we wish to let a very sudden current act upon a living object, we employ exclusively the breaking induction-shock. The intensity of the induction-shocks may be graduated by the distance that is allowed between the primary and the secondary coils. The intensity is less with greater distance, greater with smaller distance, and greatest when the secondary coil, which is always made somewhat the larger, is shoved completely over the primary.

The sledge-inductorium of du Bois-Reymond, which is one of the most essential of all pieces of physiological apparatus, is constructed, in accordance with the above principles, for the production of induced currents ; in it the secondary coil slides upon a sledge-like track (Fig. 196). It is arranged also to produce single induction-shocks rapidly and rhythmically. The contrivance that makes this possible is the Neef or Wagner hammer (Fig. 195), which is based upon the following principle. As is well known, the galvanic current has the peculiarity of transforming into a magnet a piece of soft iron, around which it flows, as long as the circuit remains closed. If the current be broken, the magnetism disappears. In Neef s hammer there is a brass column S, which bears a straight spring. This spring, to the free end of which is fastened a small hammer of soft iron, in its resting position touches an adjustable screw T, which is in connection with a wire P\ the wire forms a coil about a soft iron rod which stands upright under the hammer, and ends in a second small brass column. The two brass columns bear screws to hold the conducting wires coming from the element E. If the current of the element be made, the following happens : the current enters through the brass column S,

passes through the spring into the screw T, through the coil P, about the iron rod, into the second smaller brass column, and then returns to the element. The result is that the soft iron rod becomes magnetic and attracts the hammer that is suspended above it. Thereby the contact of the spring with the screw T is broken. By the breaking of this contact, however, the current is broken, the magnetism in the soft iron rod consequently ceases, and the hammer springs up by reason of the tension of the spring. As a result of this the spring again touches the screw T, and the current is made again. By this ingenious contrivance, as long as the element remains in the circuit, the current is continually made and broken in rapid rhythmic succession. In du Bois-Reymond's sledge-

apparatus (Fig. 196) such a hammer is inserted into the primary circuit, and by its play there occurs in the secondary circuit for every opening and every closing an induction-shock ; thus a rapid succession of shocks takes place. When sent through living substance, these act as rapid intermittent stimuli and produce a tetanus. For the construction of most of these pieces of apparatus we are indebted to the inventive genius of du Bois-Reymond alone, who has created a method that has become, and will remain, indispensable in many fields of physiology.

We will now pass from this excursus regarding the technique of galvanic stimulation to the effects that the galvanic stimulus exerts upon living substance. It is a noteworthy fact that, although electrical stimulation is one of the most common methods in use in physiology, it has been employed almost exclusively upon the nerve- and the muscle-fibre, and only occasionally upon plant-cells and unicellular organisms. This fact is associated with the one-sided development of physiology as the science of the organs of vertebrates. If experiment be limited to the organs of the higher animal body, where almost all tissues depend upon the nervous system, stimulation of the tissues may be indirect, through the nerves supplying them ; in most cases it is necessarily so, since the extremely finely branched nerve-fibres lying between the tissuecells can be excluded with difficulty. Methods of excluding completely the influence of the nervous system are known only in the case of muscle, by means of the very remarkable arrowpoison of the Mexican Indians, curare. The cells of gland-tissue, mucous membranes, connective tissue, etc., cannot be freed from the influence of the nerves supplying them, and hence, if an electric current is allowed to act upon them, because of the much greater irritability of the nerve-fibres there is always obtained not a direct stimulation of the tissue-cells alone, but a simultaneous stimulation of the nerve-fibres which transmit their own excitation to the gland-cell, the connective tissue-cell, etc. In order to put a tissue into activity by stimulation, it is of course :sufficient, and it is very convenient, to stimulate it indirectly through its nerves ; but the effect of a direct stimulation of the tissue itself cannot thus be studied. It follows that all the innumerable experiments with electrical stimulation upon the vertebrate body have to do almost exclusively with stimulation of nerve or muscle.

This fact has led to many erroneous ideas regarding the excitation-effects of galvanic stimulation. When attention was confined chiefly to the stimulation of muscle, whether directly or indirectly through the nerve, it was customary to consider contraction as the expression of excitation in the muscle. This was undoubtedly correct. But the more or less manifest thought was incorrect, that excitation exists only where contraction appears, and that no excitation is present where there is no contraction. This view has led to very many errors, many of which are not yet corrected. Thus, the idea is still maintained by many physiologists, that only variations in intensity of the galvanic current act to stimulate, and only these when they occur with a certain rapidity ; i.e., that only an increase or diminution in the strength of the current, taking place at a certain rate, produces reactions, and not a current continued with a constant intensity, or one that is very gradually increased or decreased. It was believed that this conclusion could be drawn from the following facts.

If a constant current be allowed to flow through a muscle or its nerve, the muscle contracts only at the moment of making, when, therefore, the intensity of the current suddenly increases; it expands again immediately, remains extended during the whole duration of the current, and at the moment of breaking, when the intensity suddenly falls, performs a second contraction. Further, if a current so weak as to be ineffective be allowed to flow through the preparation and then its intensity be gradually increased, it can be made very strong without the muscle making the slightest contraction. But, if a current of the same intensity be allowed to act suddenly upon the preparation, there is an energetic contraction at the making. Likewise by induction-shocks a much stronger contraction is obtained upon breaking, when, as has been seen, the electric tension is equalised suddenly, than upon making, when the equalisation takes place more slowly. These and similar phenomena have led to the mistaken idea that only the variation of a current at a certain rate acts as a stimulus, and not the continued constant current, and there has been an inclination to transfer this idea to other varieties of stimuli. This error is not unnatural in view of the facts that for a long time muscle was the sole object employed for experiment, and contraction represented the sole obvious expression of the excitation. More careful investigation has shown that during the continuance of a constant current the muscle goes into a peculiar condition which du Bois- Reymond has termed electrotonus, and in which its irritability is peculiarly changed. It has also been known for a long time that in the employment of somewhat strong currents the muscle does not extend completely after the making, but continues during the whole duration of the current in a state of feeble closing tetanus. An attempt, involving great effort and trouble, has been made to interpret this latter fact otherwise, and also many other facts that favour the idea that the muscle can be in a state of excitation without showing a sudden twitch or continuous contraction.

If experiments had not been limited to the muscle or the nerve, but if other objects, such as unicellular organisms, which express excitation in a greater variety of ways, had been employed, and if the question had been followed comparatively, this error, that stimulation results only from variations in the current, and not from the current itself, would evidently have been avoided. The one-sided study of galvanic stimulation in muscle and nerve has led to another incorrect idea, viz., the general law of polar excitation of living substance by the constant current. If a constant current be allowed to flow through a living object, it is observed that the whole stretch passed through by the current is not stimulated simultaneously, but that the excitation appears primarily at the place of entrance or outgo of the current, that is, at the anode or the kathode ; from here it can spread secondarily over the whole object because of the continuity of the living substance. Hence the anode and the kathode are the only places where the current stimulates directly; but under what circumstances the former is the point of excitation, and under what the

latter, has been reduced to a very definite principle, and this principle finds expression in the law of polar excitation. If a constant current be sent through a motor nerve, the nerve becomes stimulated at the kathode upon making, and from here the excitation extends through the conducting nerve to the muscle, which latter then performs a contraction. Upon breaking the current the excitation of the nerve takes place at the anode and extends from here to the muscle, so that the latter contracts. In the year 1859 Pfliiger confirmed this law of polar excitation of the nerve. Its correctness can be proved in various ways, best by the following experiment. A constant current is allowed to flow in different directions through the nerve of a nerve-muscle preparation, first, descending, i.e., with the anode lying nearer the central end of the nerve, the kathode nearer the muscle, and, secondly, ascending, i.e., with the anode lying nearer the muscle and the kathode nearer the central end of the nerve ; and both times the contraction of the muscle is recorded upon the plate of a myograph.1 It is then found from the length of the latent period that at the making of the descending current the muscle contracts earlier than at the making of the ascending current, but that at the breaking the relation is reversed ; the difference in time equals the duration of the process of transmission of the stimulus along the intrapolar stretch of nerve. It thus appears that the excitation upon making must start from the kathode, and upon breaking from the anode. This law of polar excitation was recognised by Bezold ('61) as valid for cross-striated muscle, and Engelmann (70) showed that it can also be applied to smooth muscle. Later investigations, especially by Biedermann (79, '83, '84, '85), afforded a number of new proofs of its validity. It was then assumed that, like muscle and nerve, all living substance is stimulated by the galvanic current at the kathode upon making,, and at the anode upon breaking.

But it has here been demonstrated again how the one-sided investigation of nerve and muscle may lead to errors, which can be avoided by comparative physiological research, for the testing of other forms of living substance, especially various kinds of free-living cells, has shown that a generally applicable law of polar excitation of living substance does not exist. Since the phenomena in question in unicellular organisms afford a striking example of the fact that excitation is caused not only by variations of current, but also by the continued current, we will here consider them somewhat in detail.

In the year 1864 Kiihne made the peculiar observation that Actinosphcerium EichJiornii (Fig. 198) obeys a very different law of excitation. But this discovery remained isolated and unnoticed for more than two decades. Only when certain other effects of the galvanic current, constituting galvanotaxis, were 1 Of. Fig. 154, p. 362. discovered, was Kiihne's observation recalled and confirmed by means of more complete methods. The examination of a long series of free-living cells followed, all of which follow a law of polar excitation differing in various ways from that of nerve and muscle.1