The Mechanistic Conception of Life

Tower was kind enough to draw for me, shows a branch which formed roots at its apex and polyps at its roots in this manner. Fig. 27. — Heteromorphosis in Margelis, a hydroid. At a and 6, where the points of stems touch the ground of the aquarium, new roots or stolons grow out. The stem touched the bottom of the dish with the apical ends, a and h. All these ends gave rise to roots. From the upper side of the original root, which was not in contact with the

Fig. 28. — Heteromorphosis in Pennaria. A piece a b of this hydroid was cut out and put into a jar with sea-water. The ends a and b touched the bottom of the jar. At both points new roots grew out. was in contact with solid bodies gave rise to roots, and every place which was in contact with seawater gave rise to polyps. in which such forms of heteromorphosis can be produced. Another form, Pennaria, is just as favorable. In Pennaria I succeeded repeatedly in producing roots at both ends of a small stem that bore no polyps (Fig. 28).^

In these experiments on Margelis and Pennaria organs brought into contact wdth solid bodies continue to grow as roots, if they grow at all. Organs surrounded on all sides by water continue to grow in the form of polyps, if they grow at all. In Margelis, contact with a solid body plays the same role as did gravitation in the case of Antennularia. In what way the contact may have an influence shall be mentioned later on, but here one more point may be mentioned. In Antennularia, gravitation not only determines the place of origin of the various organs, but also the direction of their growth; the stem, growing upward, is negativelj' geotropic, the root, growing downward, is positively geotropic. In Pennaria, the nature of the contact not only determines the place of origin of the various organs, but also the direction of their gro\\'th. If we bring an outgrowing pol^-p of Pennaria into contact with a solid body, the polyp begins to grow away from the body, and the new stem is very soon nearly' perpendicular to the part of the surface with which it came into contact.

1 In a Tubularian I was able to produce the opposite result, namely, to get an animal that ended at both ends in a polyp and had no root. Weismann seems to assume, in his Germ Plasm, that the latter result is to be explained by the principle of natural selection, inasmuch as an animal without polj-ps could not continue to live, and hence it would be impossible to produce roots at both ends. In Pennaria this supposed impossibility was realized; one may say that these roots in Pennaria may give rise later on to polyps. In the special case that I observed they did not, although as a rule they do; but the same is the case in Tubularia, in which polyps also arise from the roots. It might be said, perhaps, that the formation of roots in Pennaria is, for some reason, absolutely necessary; but it is just as easy to produce polyps at both ends. Even if it were possible to reconcile these facts with the principles of natural selection, causal or physiological morphology would not gain thereby, as the circumstances that determine the forms of animals and plants are only the different forms of energy in the sense in which this word is used by the physicist, and have nothing to do with natural selection.

may speak of positive stereotropism in the case of the root, and of negative stereotropism in the case of the polyp. Here, too, we may ask whether the contact with foreign bodies, which in these experiments determines the arrangement of the various organs, may not have the same effect in the natural development of the organism. I believe that such is the case. Negative stereotropism forces the polyps to grow away from the ground into the water, and hence parts surrounded by water form polyps only. Positive stereotropism forces roots in contact with the ground to hold to it, hence parts in contact with the ground give rise to roots only. Thus it happens that, under ordinary circumstances, in this animal we find roots only at the base where it touches the ground. In other hydroids the place of origin of the different organs is determined by light, and in others we find more complicated relations.

It may appear from the foregoing that such cases of heteromorphosis are confined to hydroids, but such is not the case. We find similar cases in Tunicates. Ciona intestinalis, a solitary ascidian, has eye-spots around the two openings into the pharyngeal cavity. If we make an incision eye-spots are formed on both sides of the incision.^ While the foregoing experiments were in progress, I observed that in many animals I was unable to produce any kind of heteromorphism. These animals showed, in regard to the formation of organs, a phenomenon with which we are familiar in a magnet. If a magnet is broken into pieces, every piece has its north pole on that side which in the unbroken magnet was directed toward the north. Likewise, there are animals every piece of which produces, at either end, that organ toward

1 Since this was written phenomena of heteromorphosis have been produced In many animals. Herbst found that in crustaceans an antenna could be caused to be formed in the place of an excised eye, Van Duyne, Bardeen, and Morgan observed phenomena of heteromorphosis in Planarians and so on (1912). in such cases of polarization. The clearest example of this I found in an actinian, Cerianthus membranaceus. If we cut a rectangular piece, c d ef, out Nothing of the sort occurs in the side c e, or d c , or f d. The production of tentacles takes place before any other regeneration begins. The same polarization is shown in the following variation of the preceding experiment. If we make an incision, acb (Fig. 30), into the body-wall of the actinian, only the lower lip, h c, produces tentacles, while the upper lip, a c, produces none. The two ends heal together in such a way that onehalf of a mouth, with its surrounding tentacles, b (Fig. 31), is formed. It is curious to see how these tentacles behave if we offer them bits of meat. They endeavor to force them into the new oral disc, where the mouth should be, and only after a struggle

in every possible way to produce tentacles in the aboral end Hydra behaves, as regards polarization, a little differently Fig. 29. — Diagrammatic. If a piece c d ef is cut out from the wall of Cerianthus, a sea anemone, new tentacles are formed only at the upper cut ef. Fig. 30. — Diagrammatic. If an incision a cb is made into the body of Cerianthus new tentacles grow out only from the lower edge c h. whole new oral pole grows out, but otherwise it too shows polarization.

A good many animals, so far as we know, reproduce only the lost organ, but never show any heteromorphism. We see, Fig. 31. — From natvire. Formation of a second head in Cerianthus after a lateral incision at b. Only a fraction of the normal number of tentacles are formed corresponding to the fraction of the periphery laid bare by the incision. No new mouth is formed, but if a piece of meat is offered to the group of tentacles at b they seize it and press it to the place where a mouth ought to be, sho\ving the purely machine-like character of all these reactions.

therefore, that while in some animals we are able to produce heteromorphosis, in others the most definite polarization exists, and we are able to produce regeneration of lost parts only in the arrangement which exists in the normal animal. In this case we must assume that unkno^Mi internal conditions determine the arrangement of limbs. In addition to examples of heteromorphosis or polarization occurring separately, we find cases in which both phenomena

are exhibited by the same animal. If we cut out a sufficiently large piece of the stem of Tuhularia mesemhryanthemum, and place it in the bottom of a dish of water, carefully protected from jarring, the anterior end of the piece gives rise to a new polyp, the posterior end to a root; but if we hang up the stem in such a way that the posterior end does not touch the surface of the glass, and is sufficiently provided with oxygen, this end, too, produces a polyp, and we have a true case of heteromorphosis (Fig. 32). In all cases the polyp at the oral end is formed first, and a relatively long time (one or more weeks) elapses before the aboral polyp is formed. Under one condition, however, I could cause the stem to form a polyp at the aboral as quickly as at the oral end, namely, by inhibiting or retarding the formation of the oral pol3rp. This could be done readily by diminishing the supply of oxygen at the oral end. In such cases the aboral polyps were produced almost as quickly as the oral polyps.^

In order to arrive at an explanation of the phenomena of organization we must ask what the physical forces are that determine the formation of a new organ. We know that the ultimate sources of energy for all the functions of living bodies Fig. 32. — Heteromorphosis in Tuhularia. From nature. Thenormal Tubularia ends at one end in a stolon, at tlie other in a head or polyp. If a piece o 6 is cut out and suspended in water a new liead or polyp c and d is formed at both ends. We can thus produce an animal wliich terminates in a head at both ends of its body; while in Fig. 28 an animal was represented which ended at both ends in a stolon or foot.

1 It was found later independently by both Godlewski and myself that if we ligature the stem of a Tubularian the polyps at both ends are formed simultaneously (1912). are chemical processes. The question is, How can these chemical forces be brought into relation with the visible changes which take place in the formation of a new organ ? The answer to this question is to be obtained by a knowledge of the mechanics of growth. It is very remarkable that the mechanics of growth forms almost an empty page in the history of animal morphology and physiology. I can refer here only to the few experiments I have made on this subject; but fortunately the subject has been worked out very carefully in plants, and as my experiments show that the conditions for growth in animals are, to a certain extent at least, the same as the conditions for growth in plants, we have the beginning of a basis for work.

A brief outline of the manner of growth in plants is as follows : Before the cell grows it forms substances which attract water from the surroundings, or, as the physicist expresses it, it forms substances which determine a higher osmotic pressure within the cell than did the substances from which the}' originate. The walls of the cell, or rather the protoplasmic layer that lines the cell-wall, possesses peculiar osmotic properties, in consequence of which it allows molecules of water to pass through freely while remaining resistant to the passing through of the molecules of many salts dissolved in the water. The result is that when substances of higher osmotic pressure are formed inside the cell, water from the outside passes in until the pressure within again equals the pressure without. The cell-wall becomes stretched and, according to Traube, new material is precipitated in the enlarged interstices, thus rendering growth permanent. This method of growth is most conspicuous, perhaps, in the germinating seed. The rising temperature in spring produces in the seed substances of higher osmotic pressure (with greater attraction for water) than the substances from which they originate. The result is that water enters the seed; by the pressure of the water within the cells their walls are stretched out and the seed grows. The chemical and

osmotic changes are the sources for the energy which is needed to overcome the resistance to growth.^ In order to ascertain whether I could determine what are the mechanical causes of growth in animals, I began at Naples some experiments on Tubularia mesemhryanthemum. I chose long stems belonging to the same colony and distributed them in a series of dishes containing sea-water of different concentrations. In some of the dishes the concentration had been raised by adding sodium chloride, and in others it had been lowered by adding distilled water. According to the laws of osmosis the amount of water absorbed by the cells of these Tubularians differed with the concentration of the sea-water, the amount being greatest in the most diluted solution and least in the most concentrated solution. If now in reality the mechanics of growth is the same for animals as for plants, we should expect that the more diluted the sea-water the more rapid would be the growth in the Tubularian stem. Of course, finally, a limit is reached where the water begins to have a poisonous effect. It was found, indeed, that within certain limits of concentration the increase in the length of the stems during the same period was greatest in the most diluted and least in the most concentrated sea-water. It is remarkable that the maximum of growth took place not in sea-water of normal concentration, but in more diluted sea-water, though this of course may not be the case in all animals. The following curve (Fig. 33) will give an idea of the dependence of growth upon the concentration of the sea-water in Tuhidaria. The values for the amount of sodium chloride, in 100 cubic centimeters of sea-water, are represented on the axis of the abscissa, the values for the increase in growth on the axis of ordinates.

These and similar experiments, which for lack of space cannot be mentioned here, show that growth in animals is 1 The substance which is formed and which causes the swelling may be an acid. I found that acids cause a swelling of muscles and it has since been shown that this is a general phenomenon. determined by the same mechanical forces which determine growth in plants. An obstacle to such a conclusion seems to lie in the fact that many plant-cells have solid walls, while this is not the case in most animal cells. The solid cell-wall, however, does not determine the peculiar character of growth. This character is determined first, by chemical processes within the cell, which result in a higher osmotic pressure, and, secondly, by the osmotic qualities of the outer layer of protoplasm, which

Pig. 33. — Curve representing the influence of diluted sea-water. The abscissae represent the concentrations, the ordinates the corresponding growth in the unit of time. The maximum growth is at a concentration between 2 and 3 per cent of salt, while the normal concentration is indicated by the vertical line between 3 and 4. allows water to pass through freely, but does not allow all salts dissolved in it to do the same. Both these qualities are independent of the solid cell-wall, and I see no reason why the animal cell should not agree in these two salient features with the plant-cell.

In order that the foregoing explanation of the mec hanism of growth in the animal cell might be based only upon knoTVTi processes, it was necessary to find out whether, in case of growth, chemical processes of such a character take place that substances of higher osmotic pressure are formed than those from which they originate. Everyone knows that by exercise our muscles increase in size. No satisfactory explanation of this fact has been given. If my interpretation of the method of g^o^^i:h were correct, I must expect that during activity substances are formed in the muscle, which determine a higher osmotic pressure than those from which they originate. This is exactly the case. Ranke had already sho\\Ti that the blood of a tetanized frog loses water and that this water is taken up by the muscles. In experiments which were carried on by Miss E. Cooke in my laboratory, we were able to show directly that during activity the osmotic pressure inside the cell-wall is raised. We determined the concentration of a solution of NaCl, or rather of a so-called Ringer's mixture, in which the gastroconemius of a frog neither lost nor took up water. We fomid that while this concentration for the resting gastroconemius was about 0.75 per cent to 0.85 per cent, for the gastroconemius that had been tetanized from twenty to forty minutes it varied from 1.2 per cent to 1.5 per cent.^

This increase of osmotic pressure inside the muscle-cell leads, during normal activity, to a taking up of water from the blood and lymph, and the consequence is an increase in volume. The same muscle, as soon as it ceases to be active, begins to decrease in size. Activity, therefore, plays the same role in the growth of a muscle that the temperature plays in the gro^\i:h of the seed. I tried to ascertain whether segmentation, like gro^iih in general, is influenced by the amount of water contained in the cell. If we decrease the amount of water in the egg of the sea-urchin segmentation is retarded, and if we use a sufficiently high concentration of sea-water it may be stopped entirely. Therefore the amount of water contained in the cell plaj^s still another role in the process of organization and influences the process of cell-division.

1 This increase in osmotic pressure is probably caused by the formation of acid. Two years after the publication of this lecture I showed that the muscle swells in an isomotic solution if this solution is acid. The recent work of Pauli and Handovski indicates that the swelling is caused through a formation of salt between the acid and a weak base, e.g., a protein. The protein salt is more strongly dissociated than the protein base (1912). The idea that the formation of the vertebrate embryo is a function of growth has been made the basis of the embryological investigations of His. In a masterly way, His has sho^\^l how inequahty of growth determines the differentiation of organs. In the blastoderm of a chick, for example, the first step in the formation of the embryo is a process of folding. There originates a head fold, a tail fold, a medullary groove, and the system of amniotic folds. According to His, all these processes of folding are due simpl}' to inequalities of growth, the center of the blastoderm growing more rapidly than the periphery. It can be shown, very simply, that such a process of unequal growth must, indeed, lead to the formation of exactly such a system of folds as we find in the blastoderm of a chick. If we take a thin, flat plate of elastic rubber, and lay it on a drawingboard, we can imitate the stronger growi:h in the center by sticking two tacks into the middle of the rubber, a short distance apart, and then pulling them in opposite directions. In this way we may imitate unequal growth, the center growing faster than the periphery. If we then fix the tacks in the drawing-board, so that the rubber in the middle remains stretched, we get the same system of folds as that shown by the embryo of a chick. I mention this way of demonstrating the effects of unequal growth as the ideas of His are still doubted by some morphologists.

His raised the question. Why is growth different in different parts of the blastoderm? But instead of trying to answer it from the physiological standpoint he answered it from the anatomical standpomt. According to him, the different regions of the unsegmented egg correspond already to the different regions of the differentiated embryo. But this so-called theory 1 Another method of producing twins from one egg is discussed in the last chapter of this book.

of preformed germ-regions gives no answer to the question, why some parts of the embryo grow faster than others. Nevertheless, it is not necessarily in opposition to the theory of growth offered in the preceding chapter. Starting with the idea of His, we may well imagine that the different regions of the ovum are somewhat different chemically, and that these chemical differences of the different germ-regions determine the differences of growth in the blastoderm. Thus the phenomena of heteromorphosis would show that, in some animals at least, the arrangement of preformed germ-regions may be changed by gravitation, light, adhesion, etc.

It must be asked, however, what, from the standpoint of causal morphology, determines the arrangement of the different germ-regions in the egg. If we answer ''heredity," causal morphology can make no use of such an explanation. Our blood has the temperature of about 37°, but although our parents had the same temperature, the heat of our blood is not inherited, but is the result of certain chemical processes in our tissues. Still it may be possible that the molecular forces of the chemically different substances of the egg determine a separation of these substances and thereby give rise to the chief directions of the future embryo.

Driesch has shown^ that by shaking a sea-urchin's egg in the four-cell stage the four cells may be separated, and each one be capable of giving rise to a complete embryo, which differs only in size from the normal embryo. If the theory of preformed germ-regions with its later modifications were true, we should expect that every one of the isolated cells would give rise to one-fourth of an embryo. But it has been said that the artificial isolation of one cleavage-cell causes a process of postgeneration or regeneration. Driesch, moreover, changed the mode of the first cleavage by submitting the ovum to one-sided pressure. In this way the nuclei were brought into somewhat

different places from those they would have held m the case of normal segmentation. Still, normal embryos resulted. One might object again that the preformation of the germ-regions existed in the protoplasm, and not in the nucleus, I have made a series of experiments to the results of which these objections cannot be made. I shall describe these experiments somewhat fully, as they have not yet been published, though I cannot enter into details at this place.

I brought eggs of a sea-urchin, within ten to twenty minutes after impregnation, into sea-water that had been diluted by the Fig. 34. — Fertilized egg of a sea-urcliin (Arbacia) put into dilute sea-water. The protoplasm swells until the membrane m bursts and part of the protoplasm 6 flows out; each of the two droplets may develop into a blastula, so that from such an egg two larvae may arise, as Indicated m Fig. 35. addition of about 100 per cent distilled water. In this solution the eggs took up so much water that the membrane (m. Fig. 34) burst and part of the protoplasm escaped in the form of a drop (6, Fig. 34), which often, however, remained in connection with the protoplasm inside the membrane after the eggs were brought back into normal sea-water. These eggs gave rise to adherent twins, the ejected part h of the protoplasm, as well as the part remaining inside the membrane, developing into a normal and perfectly complete embryo. The part of the protoplasm, which at first had connected the two drops, formed the part where the twins remained gro\Mi together. Of course, it often happened that, by accident or rapid movement, the twins were separated, and they then developed into perfectly normal single embryos. Since we caimot assume that in every case the

same part of the protoplasm escapes, we must conclude that every part of the protoplasm may give rise to fully developed embryos without regard to preformed germ-regions.^ In many eggs a repeated outflow of the protoplasm takes place. In such cases each of the drops of the protoplasm may give rise to an embryo, and I obtained not only double embryos, but triplets and quadruplets all grown together. It is remarkable that the development of these monstrosities goes on nearly at the same rate as that of the normal embryo, provided they are equally well supplied with oxygen and equally protected from microbes and infusoria. The development in most eggs takes place in so regular and typical a manner that it seems as if there were a prearrangement of some kind. It is, however, perfectly well possible that this prearrangement consists in a separation of different liquid substances in the ovum by the molecular qualities of these liquids. Such a separation, of course, might be called a preformation of germregions, but it would be something totally different from what is now understood by that term.

1. All life phenomena are determined by chemical processes. This is equally the case whether we have to do with the contraction of a muscle, with the process of secretion, or with the formation of an embryo or a single organ. One of the steps that physiological morphology has to take is to show in every case the connecting link between the chemical processes and the formation of organs. I have tried to show that in a few cases at least this connecting link was to be sought in the changes of osmotic pressure determined by the chemical changes which take place in the growing organ.

I In the light of more recent experiments it is possible, that after all only such pieces can develop into a normal embryo which contain the different germ-regions differences in the forms of organs. In order to understand this we must bear in mind that the processes of growth must necessarily be different for different organs, as for example in the formation of a root, and the formation of a stem. As growth is a process in which energy is used up in overcoming the resistance to growth, differences of growth can only be determined either by differences in the amount of energy set free in the growing organ or by differences in resistance. Differences in the energy must be the outcome of differences in the chemical processes which determine growth. Therefore we are led to the idea that differences in the forms of different organs must be determined by differences in their chemical constitution, or, if the chemical constitutions be similar, by differences in resistance to growth. That organs which differ in shape are very often chemically different is a well-known fact. The formation of urea in the liver and the synthesis of hippuric acid by the kidneys are the consequences of chemical differences.

In this way we are led through the mechanics of growth to a conclusion which forms the nucleus of Sachs's theory of organization, namely, 'Hhat differences in the form of organs are accompanied by differences in their chemical constitution, and that according to the principles of science we have to derive the former from the latter." According to Sachs there are at least as many ''spezifische Bildungsstoffe " in a plant as there are different organs.^