General Physiology: An Outline of the Science of Life

the place of its origin. According to him the transformation of a part of the heat into mechanical energy comes about by the shortening, as the result of being heated, of elements that are capable of swelling. In the last assumption he relies upon the two facts, that all positive, uniaxial, doubly-refracting substances, if capable of swelling, upon doing so shorten in the direction of their optical axis, and that bodies that are capable of swelling do so more when they are heated. According to Engelmann's investigations there exist in the anisotropic substance of muscle positive, uniaxial, doubly-refracting elements ; and, as Engelmann likewise has shown, in the contraction of muscle liquid substance passes over from the isotropic, more liquid mass of the muscle-segment into the more solid mass of the anisotropic disk, so that the latter increases in volume. Engelmann supposes, therefore, that in excitation of muscle the elements of the anisotropic muscle-substance, which he terms " inotagmata," swell as a result of the heat derived from chemical energy and shorten, so that a contraction of the muscle results. Engelmann endeavours to make his idea especially clear by an experiment, in which the contraction of muscle is imitated, according to the thermodynamic principle, by the thermal swelling and shortening of catgut. In a beaker filled with water there is a stretched violin-string which is surrounded by a coil of wire and is connected with a writing-lever. By the making of an electric current the coil can be heated, so that heat is communicated to the string.. The result is that the string swells and shortens and performs a certain amount of work by raising a weight. Upon the breaking of the current and cooling of the coil the string is extended again.

Through its ingenious simplicity this experiment makes Engelmann's view extremely clear, and it is not to be doubted that at first sight it prepossesses one in favour of the thermodynamic theory. Nevertheless, there' are many arguments against the latter, and various weighty objections to it have been brought forward, especially by Fick ('93, 1, 2). Unfortunately it is impossible to discuss here the various difficulties that lie in the way of accepting Engelmann's theory. One only may be mentioned briefly, because its consideration leads to another view which, upon the basis of microscopic facts, is connected with the chemical theories of muscle-contraction. It must be demanded of a theory of muscle-contraction that its principle shall hold good for the explanation not only of muscular movement, but also of all other forms of contractile phenomena, i.e., for protoplasmic and ciliary movements also. " Since these are united by close transitions with one another and with muscular movement, the same explanatory principle must be able to find employment in all." But the above theory does not wholly correspond to this first and foremost requisite, which Engelmann himself puts forward. It is not able, e.g., to explain the motile phenomena of amoeboid

protoplasmic masses. These simplest of all contractile phenomena offer insuperable difficulties to Engelmann's view. In order to bring the phenomena of amoeboid movement into harmony with his theory, Engelmann (79, 1) is forced to the assumption that in amoeboid protoplasm also the contractile elements have an elongated form and are capable of swelling so as to become spherical. But this assumption made ad hoc is not only not based upon facts, but is unable really to explain the phenomena. In spite of careful investigation Engelmann has not succeeded in finding in amoeboid protoplasm doubly-refracting elements similar to the fibrous structures of muscular substance. The observation that in Actinosphcerium the pseudopodia have a doubly-refracting axial strand, is not applicable, because this axial strand has nothing whatever to do with contraction ; it is simply a track upon which the contractile protoplasm can flow, and hence is analogous to the rays of the radiolarian skeleton, which are very wide-spread, especially in the Acanthometridce. But, even if the contractile protoplasm of Rhizopoda consists of numerous elongated elements that become spherical upon swelling, the extension of the extraordinarily long and slender thread-like pseudopodia that characterise most Foraminifera and Radiolaria and numerous fresh-water Rhizopoda, would be wholly inconceivable upon this assumption. These varieties of pseudopodia are formed simply by the extension of the shorter, blunt or incised processes of an Amoeba or a leucocyte. Even the formation of these latter pseudopodia cannot be explained according to Engelmann's view.

How is the occurrence of even a moderate change of form of the Amceba body to be imagined through the simple extension of numerous elements which are of a size far below the limit of perceptibility and, as Engelmann himself assumes, lie irregularly among one another pointing in all directions ? These difficulties are insurmountable. We have here arrived at the point where the problem of the movements of contraction can first be taken into consideration with reference to the result. In the amoeboid cell there is the most primitive form of contractile substance ; here the relations are undeniably much simpler than in the fibrous forms with their complex differentiations. Moreover, the phenomena exhibited by the living object can be investigated experimentally with incomparably more ease in the free-living and relatively large protoplasmic masses of amoeboid cells, than in the very small constituents of the muscle, which, separated from continuity with their neighbours, invariably perish in a very short time.

Hence, we will consider, first, the amoeboid movement of naked protoplasmic masses.1 As has already been seen,2 the element common to all phenomena of contraction is the alternation of two opposed phases, one of contraction in which the surface is diminished in proportion to the mass, and one of expansion, in which the surface is increased. In amoeboid movement expansion is expressed in the extension of pseudopodia, and contraction in their retraction and the endeavour to assume a spherical form (Fig. 268). The interchanges between the two constitute the whole phenomenon of amoeboid movement. As is well known, a naked protoplasmic drop, for example an Amceba-ce\l, behaves physically like a liquid. Its movements must, therefore, obey the general laws of liquids, as Berthold ('86) especially has consistently applied them to numerous special cases. Physically considered, every movement of a drop of liquid is the expression of changes of surface-tension, i.e., of the energy of cohesion with which the individual particles in a freely-suspended drop attract one another. If the surface-tension is equal at all points, the drop assumes a spherical form. If for any reason it is diminished in one place, there occurs there as the result of pressure from the other sides a protuberance which increases until equilibrium is again established. If the surface-tension at the same place becomes greater, the protuberance diminishes correspondingly. Hence, the spherical form of an amoeboid cell is the expression of a surface-tension equal at all points ; the extension of pseudopodia at local-, ised places is the index of a diminution of surfacetension at those places.

In other words, the problem of amoeboid movement thus made clear is contained in the question : what causes, on the one hand, a diminution of surface-tension (extension of pseudopodia), and, on the other, an increase of surface-tension (retraction of pseudopodia and tendency toward a spherical form) ? Regarding the manner of diminution of surface-tension, Ktihne's experiments ('64) upon Amoeba and Myxomycetes, already spoken of, are decisive. When Kiihne placed a drop containing Amcebce in a medium that contained no oxygen, but was indifferent in other respects, as, for example, hydrogen, the amoeboid movement gradually ceased, and the Amcebce maintained the forms that they had already assumed. If oxygen were then allowed to enter, the movement began again, new pseudopodia were extended and the Amcebce resumed their creeping. Kuhne's experiments upon the plasmodia of Myxomycetes are equally clear. He put a lump of a dry plasmodium of Didymium in a vessel filled with water containing

FIG. 268.— Amoeba in outline; the nucleus lies in the interior. A, Extending pseudopodia in various directions ; S, creeping in one direction tracted into a ball. no oxygen. In this condition no pseudopodia were formed for days. When, however, he let a few small bubbles of air into the vessel, the extension of pseudopodia immediately began, and after five hours the lump of protoplasm had extended upon the inner wall of the vessel into a richly-branched network. It is evident from this that it is the chemical affinity of certain portions of the protoplasm for oxygen that diminishes the surface-tension at definite places, and so leads to the formation of pseudopodia. With unilateral action of oxygen this must lead to positive chemotaxis, as has actually been demonstrated by Stahl ('84) in naked protoplasmic masses. As regards the manner in which the chemical affinity of the protoplasmic particles for the oxygen of the medium diminishes the surface-tension of the drop, it may at least be imagined that by the introduction of the oxygen-atoms into the biogen-molecules the cohesion of the latter is diminished.

In non-living nature there is a very striking analogue of the fact that amoeboid changes of form and movements are caused in a drop by the chemical affinity of certain constituents of the drop for substances in the surrounding medium. This is afforded by the interesting experiments of Gad ("78) upon the behaviour of oildrops in alkaline media, which later were studied by Quincke ('88). It is well known that rancid fats and oils contain molecules of free fatty, or oily, acids between the molecules of pure fat or oil. Upon contact with alkalies these acids combine with them to form soluble soaps. Hence, if a drop of rancid oil be put into a feebly alkaline liquid, a continual formation of soap takes place at the surface of contact of the two. Thereby the surface-tension is diminished locally here and there, and there results a genuine formation of pseudopodia by the oil-drop. By varying the alkalinity of the medium and the amount of free acids in the oil-drop, a great variety in the forms of the processes can be produced, many of the latter presenting a startling similarity to the forms of pseudopodia jrf certain Rhizopoda (Fig. 269).

If, thus, by the chemical affinity of certain particles of a drop for substances in the surrounding medium the surface-tension is diminished, vice versa an increase of surface-tension must come about by increased attraction between the particles of the drop. Such an increase of cohesion between the biogen-molecules themselves, or between them and other constituents of the cellbody, is comprehensible when it is borne in mind that the extent of the molecular attraction is influenced by changes in the chemical constitution of the molecules. It has been seen above that the cohesion is diminished by the oxidation of the latter. If now they be decomposed, the idea is strongly suggested that this profound change in their chemical constitution is associated with an increase of cohesion.

Upon the basis of this idea, the following picture may be drawn of the mechanism of amoeboid protoplasmic motion. Starting from the spherical form of the amoeboid cell, the surface-tension would be locally diminished at any desired point of the periphery by the introduction of oxygen into the biogen-molecule ; the protoplasm would be bulged out ; and since new biogen-molecules would thus constantly come into contact with the oxygen of the FIG. 269. — Various forms assumed by oil-drops in an alkaline liquid.

surrounding medium, a longer or shorter pseudopodium, according to the peculiar character of the protoplasm, would form. The phase of expansion would thus be mechanically explained. By the introduction of oxygen the biogen-molecules would then have reached the maximum of their labile constitution. They would then become decomposed, to a certain extent spontaneously, but more through the action of stimuli that excite dissimilation. With their decomposition the surface-tension would increase, and the stimulated protoplasm would necessarily flow back centripetally, so that the pseudopodia would be retracted — a phenomenon that is called out in a very characteristic manner by all sorts of stimuli. Thus the phase of contraction would be mechanically explained. After their return to the central cell-body the biogen-molecules would have an opportunity to regenerate themselves with the aid of substances produced by the protoplasm and the nucleus, which are absolutely necessary to the intact life of the cell ; then after the introduction of oxygen they would begin their course anew.

In accordance with this idea, all the special phenomena exhibited by amoeboid protoplasmic masses in their movement may be understood. The necrobiotic phenomena of naked protoplasmic masses especially, which can be followed very beautifully in amputated, non-nucleated, hyaline pseudopodia of Difflugia FIG. 270. — Difflugia lobostoma, with two pseudopodia projecting from the sand-capsule, the larger of which is amputated. Beside it, the changes which the separated mass of protoplasm passes through in the course of a few hours are shown from the left above to the right below. At first, normal movement with formation of pseudopodia, finally, death in the spherical form.

(Fig. 270), may be explained at once : the continuation of the amoeboid motion at the beginning, the gradual cessation of the formation of pseudopodia, and finally death in the spherical, contracted condition.1 At the beginning, immediately after the amputation of the mass, a quantity of nuclear and protoplasmic substances, which the biogen-molecules need for their regeneration, is available in the protoplasm ; the extension and amalgamation of the pseudopodia proceed at first normally. But gradually these substances are consumed, the oxydized biogen-molecules become decomposed, the pseudopodia retract, the regeneration of the biogens becomes impossible, and the incomplete biogen-residues are incapable of oxidation. Hence new pseudopodia are no longer formed, and, when all the oxidized molecules are decomposed, the mass perishes without any further change of its spherical form.

The above-developed idea of the mechanism of amoeboid protoplasmic movement has at once the great advantage that, though modified by special conditions in individual cases, its principles may be applied to all other phenomena of contraction, to protoplasmic streaming in plant-cells as well as to ciliary and muscular movement. We will here select only the most complicated case, the movement of cross-striated muscles. Since the same processes go on in all the individual muscle-segments, we will limit ourselves to consideration of the single segment. As has already been seen,1 the muscle-segment consists of two different substances, the more solid, anisotropic substance lying in the middle, and the isotropic substance lying at the two sides of the latter (Fig. 271). The phenomena that are visible with the microscope during a contraction resulting from stimulation, as Engelmann2 and others have established in detail, consists essentially in the flowing of isotropic substance from both sides into the anisotropic ; thus the latter substance increases

FIG. 271.— Muscle-segments. /, At rest, //, in contraction ; A, in ordinary, £, in polarized light, a, Anisotropic, i, isotropic disks. in volume and the disk becomes broader, while the length of the whole segment decreases correspondingly. Hence the elementary fundamental phenomenon in muscle-contraction is a mixing of two substances which at rest lie beside one another ; constituents of the isotropic, or more mobile substance, force their way into the anisotropic, or fixed substance. In this process the fact, which E. A. Schafer ('91, 1, 2, 3,) discovered, is noteworthy, namely, that the anisotropic substance, which does not change its place, offers the greatest possible surface to the entrance of the isotropic substance by means of the system of tubes already mentioned,3 so that the intermingling is able to take place very rapidly (Fig. 272). During the explosive decomposition of the biogens, either in the isotropic or the anisotropic substance, which latter is regarded by Engelmann as the specially contractile element, the chemical constitution of the biogen-molecules is so changed that a molecular attraction arises between them and certain

constituents of the other substance. As a result of this, the surface-tension between the two disks must necessarily diminish (or even become zero) ; i.e., an intermingling, a mutual penetration of the two substances must take place. In this process the isotropic, as the more mobile, substance will necessarily diffuse into the anisotropic, as the more fixed, i.e., the muscle-segment will necessarily decrease in length and increase in breadth. There will thus be in principle the same process as in swelling, except that, as Engelmann assumes, there will be, not a simple admission of water, but a chemical swelling, in which along with the water other chemical substances will enter, especially such as take part in the regeneration of the decomposed biogen-molecules. But in proportion as these molecules are regenerated and by the introduction of oxygen are brought back to the maximum of their labile constitution, a change in the molecular relations occurs, and now, in contrast to what happened previously, a separation of the two substances will take place, which will give to the muscle-segment its original form. Although the processes, which for the present are wholly unknown, may in reality take place very differently, at all events the principle of modification of the molecular attraction by changes in the chemical constitution of the molecules, the same principle that explains amoeboid movement, appears to be able to elucidate in its essential points the obscure phenomenon of muscular movement. Thus, contraction-movements in their most essential points are controlled by the direct interchanges of chemical and mechanical energy without the mediation of another form of energy, such as heat or electricity.

Here consideration of the mechanism of contraction-movements merges with that of the changes of energy in muscle activity, and we arrive again at the view already reached by an entirely different path, namely, that the activity of muscle depends upon the alternation of the decomposition and regeneration of living protoplasmic particles. We have now reached the end of our inquiry into the mechanics of cell-life. Starting from the idea that in metabolism lies the real vital process, which is expressed in the manifold vital phenomena, we endeavoured to trace back the elementary vital phenomena of the cell to the chain of metabolic processes, by which the individual parts of the cell are united with one another and with the external world. Our last discussion, that of movemerit in the cell, affords the best example of how the changes of

FIG. 272. — Muscle-segment of the wasp containing tubes of anisotropic substance. a, Anisotropic disk seen from above ; 6, seen from the side ; c, three musclesegments. (After Schafer.) form and energy are inseparably connected with the changes of substance, how all three in reality form a single whole, which offers merely different sides for consideration. So far as scientific knowledge renders it possible, an attempt has been made to solve the problem. Naturally many suppositions and many hypotheses have been found necessary to close the wide gaps in our present knowledge, and in spite of this many recognized gaps still remain open. But cell-physiology, aided by the stern necessity of its development, and its great working power, is beginning to give encouragement to the highest expectations.

So far, in all our investigations, experiments, discussions and theories the individual cell, as the independent elementary organism, has been the chief object of interest. Now, in terminating pur long examination of the physiological problem, it remains to examine the mechanism resulting from the association of the cells in a community. The life of the multicellular organism is not a simple summation of the lives of the individual cells which compose it ; many special relations are inaugurated by the association of the individual cells, and these are expressed in the vital phenomena of the multicellular organism.

It has been seen elsewhere 2 that the size of the individual cell is necessarily limited. From this fact an important consequence follows. A large organism can never be formed by a single cell, it must be constructed from many cells. All large organisms are cell-communities. By the union of the individual cell with others of its like, relations are presented that influence the life of the former so that its vital phenomena are different from what they are when it lives free. As in the formation of every community, the formation of that composed of cells requires a compromise between individuals. The compromise consists in the fact that every cell gives up a part of its independence for the advantage that it derives from association with other cells. The special form of this compromise between the individual components is very different in different cases. In the cell-communities of the series of organisms we find realised a much greater variety of forms of government than we see developed in human society, and it would

1 [The word " state," as employed in Political Science, carries with it the idea that the association of individuals thus designated is a self-conscious association. (Gf. Giddings: The Principles of Sociology, New York, 1896.) I have thought, therefore, that in the present book the author's term "Zellenstaat " would preferably be translated, not "cell-state," but " cell-community." — F. S. L.] be very profitable to treat modern sociology in the light of these. If this were done, doubtless many schemes regarding social reform would result very differently from at present.

In a cell-community there is nothing living but the cells. The life of the community is merely the expression of the lives of the cells. Hence it is evident that a cell-community can live only when its individual constituents lead suitable lives. The independent vital activity of the individual cell is, therefore, the indispensable prerequisite of the life of the compound organism. But how much of its independence the individual cell gives up in uniting with others is subject to great variation. That it must always give up something is evident when it is borne in mind that by the association of the different cells the external vital conditions of the individual cell become greatly changed. Cells that have permanently exchanged free individual life for life in a cell-community, such as the tissue-cells of the higher plants and animals, usually perish very soon when separated from their associates. The other cells of the community become an external vital condition for the tissue-cell.

This condition of dependence in which the cells of the community stand to one another is less, and the independence of the individual cell is greater, the lower we descend in the series of organisms, the more the individual cells of the community resemble one another. The simplest relations are found among the Protista. Here we find cell-communities of the primitive type of a genuinely republican form of government, in which every cell is like the others and is capable of existing by itself independently of the others. A Carchesium stalk (Fig. 273, /), a Eudorina colony (Fig. 273, //, A }, and a Magosphcera globule (Fig. 273, //, B}, are such true cellrepublics. Sometimes the members of these communities separate themselves from one another and lead an independent life. But, so long as they are united, a certain dependence exists even in the genuinely republican community, in spite of the great independence of the individual cells. The individual Carchesium is influenced by its neighbours. If one of its neighbours suddenly contracts, it is likewise made to contract by the shock. The individual Eudorina- or Magosphcera-cell in its movement is likewise dependent upon the others. The stroke of its cilia does not drive it to the place where it would swim if it had free locomotion, but is only one of the many components from which the movement of the whole spherical colony results.

But the dependence of the cells is much greater in the cellcommunities of the plants and the lowest Ccelenterata, which stand upon the same social grade with the plants, than in these cellrepublics of the Protista. The government of plants has also been termed republican, in contrast to the more monarchical government of animals. This designation is correct, but the government of the cell-communities of plants, sponges, and hydroid polyps is not the primitive form of a republic, which has been seen in the colonies of the Protista. We find here no longer the power of the individual cell to exist by itself apart from association with the

FIG. 273.— /, Carchesium polypinum, a stalk of Ciliata. A, The individuals are extended upon their stalks. B, The individuals have contracted as the result of a shock. //, A, Eudorina degans a colony of Flagellata ; B, Magosphcera .planula, a colony of Ciliata. (After Haeckel.) others. Dependence upon the other cells is too great, but small groups of cells can maintain themselves and live separately. E.g., as Vochting ('85) has shown, the leaves of many plants can be cut into minute pieces and from them whole plants can grow, and likewise, as has been seen (Fig. 2, p. 57), every piece of a Hydra, that has been cut up is capable of independent life.

The dependence of the individual cells upon one another in many tissues of the higher animals is still closer than in the plants and the lowest C&lenterata. Here a pronounced despotism prevails. The constitution of ciliated epithelia affords an interesting example. As is well known, a ciliated epithelium consists of many successive rows of ciliated cells arranged one after another in each row, and each cell possessing a number of cilia (Fig. 274, /). The cilia of these cells are in rapid, rhythmic vibration, but it is seen that the ciliary motion of the individual cells of one row is not irregular and independent of the others ; there exists a

FIG. 274.— Ciliated epithelium. /, Three ciliated cells connected with one another, from the epididymis. (After Schiefferdecker.) II, Beroe ovata, with the four rows of ciliary plates upon one side. ///, Row of cilia of a Beroe seen from the side. At * a plate is fixed by being bent back by means of a small scalpel, so that it cannot contract. As a result of this, the ciliary waves pass from above only to this plate, while the plates below it are at a standstill.

metachronism in the ciliary stroke 1 in such a manner that the cilia of all the cells contract in regular succession, beginning with the end-cell of the row. This phenomenon can be observed much better in the rows of ciliary plates in the Ctenophora (Fig. 274, II) than in the microscopic ciliated epithelium of the vertebrates. In the former, where the ciliary plates are to be seen very distinctly with the naked eye, and where the movement goes on often very slowly, it is readily observed that every plate moves only when the preceding one has moved, and then remains at rest until a new wave comes from the first plate. If such a row with the under-

lying tissue be excised from a Beroe, a preparation is obtained in a form easy to study. The movement begins in the uppermost plate and proceeds to all the succeeding ones. If the uppermost plate is at rest, so are all the succeeding ones ; a plate in the middle of the row never contracts while the preceding ones are at rest. If a plate in the middle of the row be held fast, the ciliary waves course from above down to this plate only ; they stop here, and all the lower plates in the series stand still (Fig. 274, ///). Thus every plate is in the closest dependence upon the one next above, and is never able to move independently. But the movement of all the plates is determined in this manner by the first plate of the series (Fig. 275, A). In spite of this, every plate possesses in potentia a certain independence. If, e.g., the row be cut through, the plate that now stands first in the series undertakes the lead, and controls by its contraction and its rest all the plates standing below it, so that the two separated halves of the

FIG. 275.— .4, Intact row of cilia showing normal metachronism of beat. The uppermost (left) cilium inaugurates the rhythm and the others follow at the same rate. B, Row of cilia divided in the middle by a cut. Each half acts with its own rhythm. row now act with separate rhythms (Fig. 275, B}. Every individual plate, indeed, taken out of the series contracts rhythmically, provided that the cell-body belonging to it is still present. There is here an interesting case of complete subordination. Every ciliated cell of an epithelium, so long as it is living, possesses in itself complete autonomy as regards its movement ; in union with its like, however, it has wholly given up the independence of its movement. This is necessary if a metachronous motion, which possesses essential advantages, is to come about. The same relation is found not only between the individual ciliated cells of an epithelium, but also between the individual cilia of a cell. In the latter the same metachronism of beat exists in a long row of cilia, as may be seen especially plainly in ciliate-infusorian cells. No cilium acts before the one preceding it in the row. If the uppermost one rests, the whole series is quiet. Nevertheless, every individual cilium, separated from the others, shows complete independence of movement. If, e.g., in Spirostomum the long row of peristome