General Physiology: An Outline of the Science of Life

work permits one phase to come more to the front, whether it be metabolism, or change of form, or transformation of energy, it is advantageous to select for the study of any vital phenomenon a specific form of cell in which the vital phenomenon in question is expressed especially clearly. By this method the phenomena of changes of substance, of form and of energy may be considered separately in different objects. But this ought never to lead us into considering these different groups of phenomena as mutually independent. They are merely different phases of one and the same process.

The number of chemical bodies that when brought into contact with living substance enter into chemical relation with its constituents is enormous, but thus far only a few of them have been investigated as regards their stimulating effects. A comprehensive, comparative, cell-physiological investigation of chemical stimuli and their actions, undertaken from a systematic point of view, would require a very long time, but would surely yield very valuable results. For the present, our knowledge of these stimuli and their effects is so full of gaps that a systematic summary of it is not possible. We must, therefore, limit ourselves to the consideration of a few typical phenomena.

In general, increase in the quantity of ingested food-stuffs acts as a chemical stimulus to augment metabolism. The best example is afforded by the cells of the various tissues of the human body, the most essential food-stuff of which is proteid. As Voit ('81) has shown, a strong man, working hard, needs 118 grs. of proteid in order to maintain his nitrogenous equilibrium intact, i.e., in order to replace the quantity of nitrogen derived from the destruction of the living substance of his cells arid excreted in the urine. If this quantity of ingested proteid, which is a necessary vital condition, be increased, as is the case with most men living under good conditions, the greater quantity is not employed for the construction of new cells, for the increase of living substance, but is taken up by the tissue-cells from the blood, passed over into living proteid and split up, to leave the body again almost completely in the urine as the products of retrogressive proteidmetamorphosis (urea, uric acid, creatinin, etc.). The increase of the proteid-income beyond a certain measure (118 grs.)accomplishes,

therefore, a corresponding increase of both the assimilatory and the dissimilatory phases of the metabolism of the tissue-cells. A similar condition exists among plants. The carbonic acid of the air serves the plant as food and is split up in the chlorophyllbodies of the living cells. The carbon set free is then employed, together with the water received through the roots, for the synthesis of starch, or assimilation. If more carbonic acid be brought to the plant than is contained in the air as its necessary vital condition, the splitting-up of carbonic acid and the assimilation of starch are increased in equal measure up to a certain degree. The increase of the quantity of food, therefore, conditions also an increase of metabolism.

But this does not always hold good. Regarding oxygen, we know, at least, that its increase in quantity beyond the amount necessary for life is essentially without influence upon the metabolism of the tissue-cells. The tissue-cells of the human body are within wide limits independent of the percentage and the partial pressure of oxygen in the air, and experience no augmentation of metabolism with increase of the income of oxygen. Whether the same is true of free-living cells and the cells of lower animals still needs investigation.

In many cases the increased income of food that is accompanied by an increase of metabolism causes also a clearly recognisable increase in change of form. While in the tissue-cells of the human body, as has been seen, the food that is introduced beyond the necessary quantity is under normal conditions destroyed excepting an extremely small fraction, and is not employed for the increase of living substance, in many unicellular organisms, especially in Bacteria and Infusoria, an increase of the assimilatory processes, and in unequal measure of the dissimilatory processes also, takes place with increase of food. The result of this is an increase of living substance, a " fattening," which is expressed in rapid growth and continued cell-division. If, e.g., putrefactive bacteria (Bacterium termo, Spirillum und.ula, etc.) be transferred from a liquid in which they are living in small numbers, into a good nutrient solution, such as an infusion of hay, they at once begin to increase enormously, until from the few bacteria with which the nutrient solution was infected many millions may have developed. If there be placed in such a hay-infusion swarming with putrefactive bacteria a Paramcetium, which nourishes itself upon such bacteria, in a few days it may be seen that from this one infusorian thousands have been produced, so that they give to the liquid a milky cloudiness. Thus the assimilatory phase of the metabolism of these micro-organisms becomes enormously increased by superfluity of food.

Under pathological conditions also similar phenomena occur in the tissue-cells of the human body, and modern pathology recognises a whole series of analogous cases in the various kinds of pathogenic neoplasms or tumours, to which belong also malignant cancers. These tumours (carcinoma, sarcoma, myoma, fibroma, etc.) arise by the rapid division of the cells of a normal tissue, e.g., the epidermis. There thus results in the particular place an enormous increase of cells, a growth, which leads frequently to a very extensive tumour and completely chokes the neighbouring tissues in which it grows, so that they become incapable of life and perish. Without doubt, in many cases this rapid cell-increase is due to chemical causes acting upon the cells in question. Although -thus far it is an open question whether or not tumours, especially carcinoma, are a result of infection by certain micro-organisms, the majority of pathologists incline to the view that they are to be traced to a change in the nutrition of the cells.

Much more evident than the effects of chemical stimuli upon metabolism and form-changes are the effects upon the transformation of energy, especially upon movement. Regarding the effects upon the amoeboid movements of naked protoplasmic masses, such as Rhizopoda, Amoeba, Myxomycetes, Polythalamia, and the protoplasmic bodies of plant-cells, the classic investigations of Max Schultze ('63) and Kiihne ('64). over thirty years ago, have afforded information. The most wide-spread effect here is

the calling-out of a contraction, i.e., the retraction of pseudopodia, frequently after a preliminary acceleration of the protoplasmic streaming at the beginning of the action. The greatest variety of chemical substances can produce this reaction. If, e.g., to a drop of water in which many amoebae exist there be added a 1 — 2 per cent, solution of common salt, or a solution of 0*1 per cent, hydrochloric acid, or of 1 per cent, potassium hydrate, or other acids, alkalies and salts in weak solution, the amoebae immediately draw in their pseudopodia and assume a spherical form (Fig. 158). Carbonic acid exerts the same effect, if the amoebae be exposed in a gas chember 1 for some time to the action of the gas. Other naked protoplasmic masses behave similarly toward these chemical stimuli. The delicate Actinosphcerium Eichhornii, which with its straight, ray-like pseudopodia appears like a minute sun, when

FIG. 158. — Amoeba. A, With pseudopodia extending in different directions. B, Creeping, with a long pseudopodium in one direction (form of Amoeba, Umax). C, Contracted to a ball upon chemical stimulation. brought into contact with these stimuli, likewise gradually draws in its pseudopodia, the protoplasm becoming contracted into numerous, small globules and spindles, which slowly flowcentripe tally into the cell-body l (Fig. 159). Upon the effect of chemical stimuli upon ciliary motion, Engelmann ('79, 1) and Rossbach ('71) especially have carried out detailed investigations. Here also the greatest variety of substances, such as acids, alkalies and salts, carbonic acid and various alkaloids, have like effects, which always consist in an augmentation of the activity of the cilia or flagella, the rate of their beat being considerably increased. The result is a considerable augmentation of the motor effect, which can be clearly observed in free-living ciliated cells, such as Infusoria, in a great acceleration of their

FIG. 159. — Actinosphcerium under chemical stimulation. A, Unstimulated ; B. at the beginning of the stimulation ; C, after the stimulation has continued for some time (the pseudopodia are almost entirely drawn in). motion. After the addition of chemical reagents the Infusoria by the strokes of their cilia rush madly through the field of view. Numerous chemical stimuli act upon the different forms of muscle-fibres (myoids, smooth muscle-fibres, cross-striated musclefibres) in a manner analogous to that upon naked protoplasmic masses, by calling out contractions. If to a drop of water in which many Vorticellce exist, waving their bodies gracefully upon their extended stalk-muscles, chemical substances of the above-mentioned kinds be added, all the Vorticellce immediately draw together, their stalk-muscles suddenly contracting in their elastic sheaths, and coiling up into delicate spirals (Fig. 160, 5). Cross-striated muscles likewise contract suddenly upon chemical stimulation. If, e.g., the sartorius muscle of a frog, which forms a small band of nearly parallel, cross-striated muscle-fibres, be clamped in a muscle-holder

by means of the attached legbones, and a thread, passing over a wheel and attached to a small weight, be drawn through the pelvic bone, to which the muscle is also attached, every movement of ' the muscle can be observed in a signalling-lever, which is fastened to the wheel (Fig. 161). If, now, a dish containing ammonium carbonate be brought under the muscle, the latter is chemically stimulated by the vapours of the ammonia, and performs contractions, which can be shown clearly by the lever and can be traced upon a smoked drum. Biedermann ('80) observed a very remarkable phenomenon in the sartorius muscle when he let it hang in a temperature of 3° — 10° C. in a solution of 5 grs. common salt, 2 grs. alkaline sodium phosphate, and 0'5 grs. sodium carbonate in one litre of water (Fig. 162). The muscle then showed rhythmic con tractions, a phenomenon that otherwise is never observed in this muscle during life, and suggests constantly the rhythmic motion of cardiac musclefibres.

The chemical effects of stimulation in contractile substances, thus far spoken of, consist of contractions. But certain chemical stimuli produce expansion. Such, e.g., are food-stuffs, and especially oxygen. These phenomena have been discussed elsewhere.1 They consist chiefly in the fact that in an atmosphere free of oxygen Amceba and marine Rhizopoda cease the formation of pseudopodia and undergo a diminution of expansory processes, developing

the latter again when new oxygen is introduced. Kiihne (I. c.) has observed the same in Myxomycetes, in the reticulate plasmodia of Didymium. which lives upon decaying leaves. When he introduced a dried, and, therefore, completely motionless, piece of the plasmodium into a vessel filled with water boiled and hence free of oxygen, which was shut off by mercury from the air, it remained in complete rest. But as soon as a few bubbles of oxygen were added to the Didymium, the latter began to extend pseudopodia and to spread itself out in an arborescent

FIG. 160.— Vorticella. a, Extended; b, contracted after chemical stimulation (the stalk-muscle is not seen) ; c, a piece of the stalk-sheath containing the muscle-fibre, strongly magnified. manner on the inner surface of the vessel. From these experiments it is very clear that oxygen acts as a stimulus, giving rise to the expansory phase of protoplasmic movement. The production of other forms of energy besides that of movement is also excited by chemical stimuli. Since it would, however, lead too far to consider all the excitation-effects of such stimuli, only the facts connected with the production of light will be presented.

FIG. 161. — Chemical stimulation of the sartorius muscle. of the frog. For the investigation of this the unicellular organisms are best fitted, for in them all conditions are simplest and most easily observed. It is known of many unicellular organisms, Bacteria, Radiolaria, etc., that they develop light as the result of chemical, as of various other stimuli. But light-production has been investigated most frequently and in most detail in the Noctilucce,

the peculiar Flagellata which usually produce the light on the surface or the water in our northern seas (Fig. 163). Recently Massart ('93) has studied again in detail the action of chemical stimuli upon them. In a vessel containing sea-water, in which the Noctilucce rested quietly upon the surface without emitting light, he placed carefully with a pipette various substances, such as distilled water, a concentrated solution of common salt, a solution of sugar, etc., and in each case let the drop spread slowly over the

surface of the seawater. The result was that as soon as the liquids introduced came into contact with the Noctilucce, the latter became brilliantly lighted, and the pleasing spectacle was presented of a slowly widening, glowing circle, spreading over the surface of the water. A similar phenomenon can be observed very well in Radiolaria, especially in the large Thalassicolla, which emits light actively upon a change in the concentration of the sea-water in

FIG. 162.— Production of rhythmic contractions in the sartorius muscle by chemical stimulation. which it exists, or upon being transferred to fresh water. The various luminous Bacteria, which produce, e.g., the luminosity of dead sea-fish, behave similarly. Finally, the living substance of nerves and ganglion-cells can be excited by chemical stimuli. The excitation in the nerve-substance itself is not visible without special methods ; but a clear expression of it in motor nerves is exhibited in the contraction of muscles supplied by them. If, e.g., the sciatic nerve of a frog be stimulated by its central end being dipped into glycerine, a concentrated solution of common salt, or a solution of a mineral acid, an alkali, a metallic salt or sugar, contractions of the leg-muscles of the frog take place, and prove that the nerve is excited. Excitation by chemical stimuli can be observed in the excised

development of electricity, which influences the current derived from the resting nerve. In contrast to the exciting effects of the chemical stimuli just mentioned are the effects of certain chemical substances, which depress or wholly suppress vital phenomena. These substances are, hence, termed narcotics or anaesthetics. Among them belong especially those that depress all forms of living substance and all vital phenomena : alcohol, ether, chloroform, and chloral hydrate. With these belong the great group of alkaloids, comprising morphine, quinine, veratrine, digitaline, strychnine, curare, etc., some of which act upon a great variety of living cells, while others affect specific cells only, especially those of the central nervous system.

The depressing effects of narcotics upon the phenomena of metabolism have been studied especially by Claude Bernard (78). This well-known Parisian physiologist showed that metabolism is suppressed by chloroform-narcosis in very different forms of cells. If yeast-cells, which, as is well known, in the course of their metabolism split up grape-sugar into carbonic acid and alcohol, be placed in two fermentation -tubes (Fig. 164), one of which contains a pure solution of grape-sugar, the other some chloroform-water mixed with a similar solution of grape-sugar, there appears at once, under otherwise completely identical conditions, in the first tube a fermentation, as is evident from the carbonic acid rising and accumulating above (Fig. 164, A), but in the second tube an entire absence of fermentation (Fig. 164, B). If the contents of the second tube be left open to the air for a time, so that the chloroform evaporates, fermentation appears there later. The chloroform-water, therefore, only inhibits the metabolism of the yeast-cells without killing them.

In plant-cells also the depression of metabolism is very easily brought about, especially the cessation of the cleavage of carbonic FIG. 164. — Fermentation experiment. A, Production of carbonic acid in a solution of grapesugar by means of yeast-cells. B, The solution of grape-sugar is not fermenting because the yeast-cells are narcotised by chloroformwater. A, Piece of a thread consisting of many cells arranged in a row. B, Single cell with the characteristic spiral band of chlorophyll and the star-shaped protoplasmic body.

acid in chlorophyll. Claude Bernard employed for this a filose, aquatic Alga, Spirogyra, the cylindrical cells of which are arranged lengthwise one after another in fine1 threads and possess a delicate, spirally wound band of chlorophyll (Fig. 165). Under two" bell-jars, of which one was filled with water containing carbonic acid, the other with water containing carbonic acid and chloroform, he placed a quantity of Spirogyra threads and exposed the jar to the sunlight. After some time the cells in the first jar had evolved a considerable quantity of oxygen, while in the second the evolution of oxygen and, therefore, the dissociation of carbonic acid, were wholly absent.

Corresponding with the cessation of metabolism, the phenomena of form-changes are also depressed in narcosis. Growth and celldivision cease. In order to prove the inhibition of growth, Claude Bernard arranged the following experiment (Fig. 166). Two empty, cylindrical flasks were provided, above and below, with openings that were closed by rubber stoppers, each pierced by a glass tube. In each of these flasks there was placed, half-way up, a moist sponge, and upon the latter sprouting plant-seeds were laid. Through the lower opening one flask («') communicated by means of a rubber tube (V) with a glass cylinder (t), which contained at its bottom a layer of ether (S) ; through the stopper of the cylinder, beside the tube V, an open glass tube (a) projected

FIG. 166. — Apparatus for the comparison of germinating plant-seeds in the normal condition and in narcosis. (After Claude Bernard.) from the outside down to one-half the depth of the cylinder. The lower opening of the other flask (e) communicated through the glass tube (a') directly with the outside air. To the glass tubes that led outside through the stoppers in the necks of the flasks, a forked rubber tube (b) was fastened, which was in connection with an aspiration-apparatus (P). If the water of the water-pipe (R) was let through the aspirator, it sucked the air through the two glass flasks, of which the one received pure air directly from the outside through the tube (a1), while the other took in through the glass cylinder (t) air charged with ether-vapour. In this way a continuous stream of pure air passed through the germinating seeds of the one cylinder and a stream of ethervapour

through the seeds of the other. After some days under this arrangement the seeds that were in pure air had grown out into long seedlings (e), while those bathed by the ethervapour showed no growth at all, without, however, having lost the capacity of germinating in pure air. The brothers Hertwig ('87) have investigated the depressing action of solutions of chloral hydrate upon cell-division in eggs of the sea-urchin. When they let a 0'2 — 0'5 per cent, solution of chloral act for some time (5 minutes — 3 hours) upon eggs that were about to develop, cell-division did not go on. Both the nucleus and the protoplasm remained in the stage of division in which they already

FIG. 107.— Mimosa pudica, in ether-narcosis. (After Claude Bernard.) were, while the formation of rays about the centrosomes was completely absent. Only after the eggs had been washed for a considerable time with pure sea-water did the development and division of the cell proceed again. Finally, the phenomena of transformation of energy are also depressed by narcosis. Both the spontaneous production of energy and the capacity of reacting to stimuli are diminished, and finally wholly cease. Among the phenomena of motion Claude Bernard has shown this for the turgescence-movements of Mimosa pudica.'1 If a pot containing a Mimosa be placed under a bell-jar, under which is a sponge soaked with ether (Fig. 167), the spontaneous move-

merits cease, and, moreover, after some time it is no longer possible to call forth by stimuli the well-known movements, which consist of a falling of the branches and a folding together of the leaves. The irritability is extinguished, the plant is in narcosis. " What a singular thing," says Claude Bernard, " plants can be anaesthetised like animals, and absolutely the same phenomena can be observed in the two." Like the turgescence-movements,the growth-movements of plants also cease in narcosis, and the secretory movements of the Diatomece, Oscillarice, and Desmidiacece l are wanting.

Contraction-movements are also depressed by narcotics ; but, as a rule, at the beginning of the influence a short stage of excitation is noticed, in which the movements are accelerated. The protoplasmic movements of Amceba cease after the cells have contracted into a ball. As Binz ('67) found, quinine especially exerts a powerful paralysing action upon the amoeboid movements of leucocytes. Engelmann ('68) carried out extensive investigations upon the depressing action of narcotics upon ciliary motion. When he let the vapour of ether or chloroform act upon the ciliated cells of the pharyngeal mucous membrane of a frog in a gas-chamber, after a rapid preliminary stage of excitation, in which the motion was accelerated, a standstill of the cilia took place. If the duration of the action was not too long, the motion appeared again after the introduction of fresh air. According to the observations of the Hertwigs ('87), similar behaviour was exhibited by the flagella of spermatozoa that had been brought to complete standstill by ether- and chloroform-vapours, as well as by small doses of quinine and chloral hydrate, so that the fertilisation of the ovum was hindered by the absence of their movements. In Infusoria also by the introduction of chloroform -water, after a short stage of excitation in which the cells whirl madly through the water, ciliary motion is inhibited. In Stentor, in addition to this fact, the paralysis of the myoids by the chloroform-water can be observed at the same time. In their undisturbed condition the Stentors are extended in the form of delicate trumpets with their aboral pole attached at the bottom (Fig. 168, A). From time to time, partly spontaneously and partly as a result of stimulation, they jerk together into stalked balls (Fig.

168, C) by the contraction of their fine myoid-fibres that extend from the upper to the lower end of the cell-body in the exoplasm. In narcosis, however, after a sudden twitch at the beginning of the influence, they assume a stage of moderate contraction (Fig. 168, B\ their cilia cease to beat, and their bodies do not shrink into the customary ball either spontaneously or upon stimulation, until by transference into fresh water the narcosis is ended. Like the smooth myoid-fibres, the irritability of cross-striated skeletal muscles also is completely abolished by narcosis. A frog's muscle