"The nucleus may even be supposed to exist in the pollen of this family.

In the early stages of its formation, at least a minute areola is of ten visible in the simple grain, and in each of the const.i.tuent parts of cells of the compound grain. But these areolae may perhaps rather be considered as merely the points of production of the tubes.

"This nucleus of the cell is not confined to orchideae, but is equally manifest in many other monocotyledonous families; and I have even found it, hitherto however in very few cases, in the epidermis of dicotyledonous plants; though in this primary division it may perhaps be said to exist in the early stages of development of the pollen. Among monocotyledons, the orders in which it is most remarkable are Liliaceae, Hemerocallideae, Asphodeleae, Irideae, and Commelineae.

"In some plants belonging to this last-mentioned family, especially in Tradascantia virginica, and several nearly related species, it is uncommonly distinct, not in the epidermis and in the jointed hairs of the filaments, but in the tissue of the stigma, in the cells of the ovulum even before impregnation, and in all the stages of formation of the grains of pollen, the evolution of which is so remarkable in tradascantia.

"The few indications of the presence of this nucleus, or areola, that I have hitherto met with in the publications of botanists are chiefly in some figures of epidermis, in the recent works of Meyen and Purkinje, and in one case, in M. Adolphe Broigniart's memoir on the structure of leaves. But so little importance seems to be attached to it that the appearance is not always referred to in the explanations of the figures in which it is represented. Mr. Bauer, however, who has also figured it in the utriculi of the stigma of Bletia Tankervilliae has more particularly noticed it, and seems to consider it as only visible after impregnation."(2)

SCHLEIDEN AND SCHWANN AND THE CELL THEORY

That this newly recognized structure must be important in the economy of the cell was recognized by Brown himself, and by the celebrated German Meyen, who dealt with it in his work on vegetable physiology, published not long afterwards; but it remained for another German, the professor of botany in the University of Jena, Dr. M. J. Schleiden, to bring the nucleus to popular attention, and to a.s.sert its all-importance in the economy of the cell.

Schleiden freely acknowledged his indebtedness to Brown for first knowledge of the nucleus, but he soon carried his studies of that structure far beyond those of its discoverer. He came to believe that the nucleus is really the most important portion of the cell, in that it is the original structure from which the remainder of the cell is developed. Hence he named it the cytoblast. He outlined his views in an epochal paper published in Muller's Archives in 1838, under t.i.tle of "Beitrage zur Phytogenesis." This paper is in itself of value, yet the most important outgrowth of Schleiden's observations of the nucleus did not spring from his own labors, but from those of a friend to whom he mentioned his discoveries the year previous to their publication.

This friend was Dr. Theodor Schwann, professor of physiology in the University of Louvain.

At the moment when these observations were communicated to him Schwann was puzzling over certain details of animal histology which he could not clearly explain. His great teacher, Johannes Muller, had called attention to the strange resemblance to vegetable cells shown by certain cells of the chorda dorsalis (the embryonic cord from which the spinal column is developed), and Schwann himself had discovered a corresponding similarity in the branchial cartilage of a tadpole. Then, too, the researches of Friedrich Henle had shown that the particles that make up the epidermis of animals are very cell-like in appearance. Indeed, the cell-like character of certain animal tissues had come to be matter of common note among students of minute anatomy. Schwann felt that this similarity could not be mere coincidence, but he had gained no clew to further insight until Schleiden called his attention to the nucleus.

Then at once he reasoned that if there really is the correspondence between vegetable and animal tissues that he suspected, and if the nucleus is so important in the vegetable cell as Schleiden believed, the nucleus should also be found in the ultimate particles of animal tissues.

Schwann's researches soon showed the entire correctness of this a.s.sumption. A closer study of animal tissues under the microscope showed, particularly in the case of embryonic tissues, that "opaque spots" such as Schleiden described are really to be found there in abundance--forming, indeed, a most characteristic phase of the structure. The location of these nuclei at comparatively regular intervals suggested that they are found in definite compartments of the tissue, as Schleiden had shown to be the case with vegetables; indeed, the walls that separated such cell-like compartments one from another were in some cases visible. Particularly was this found to be the case with embryonic tissues, and the study of these soon convinced Schwann that his original surmise had been correct, and that all animal tissues are in their incipiency composed of particles not unlike the ultimate particles of vegetables in short, of what the botanists termed cells.

Adopting this name, Schwann propounded what soon became famous as his cell theory, under t.i.tle of Mikroskopische Untersuchungen uber die Ubereinstimmung in der Structur und dent Wachsthum der Thiere und Pflanzen. So expeditious had been his work that this book was published early in 1839, only a few months after the appearance of Schleiden's paper.

As the t.i.tle suggests, the main idea that actuated Schwann was to unify vegetable and animal tissues. Accepting cell-structure as the basis of all vegetable tissues, he sought to show that the same is true of animal tissues, all the seeming diversities of fibre being but the alteration and development of what were originally simple cells. And by cell Schwann meant, as did Schleiden also, what the word ordinarily implies--a cavity walled in on all sides. He conceived that the ultimate const.i.tuents of all tissues were really such minute cavities, the most important part of which was the cell wall, with its a.s.sociated nucleus.

He knew, indeed, that the cell might be filled with fluid contents, but he regarded these as relatively subordinate in importance to the wall itself. This, however, did not apply to the nucleus, which was supposed to lie against the cell wall and in the beginning to generate it.

Subsequently the wall might grow so rapidly as to dissociate itself from its contents, thus becoming a hollow bubble or true cell; but the nucleus, as long as it lasted, was supposed to continue in contact with the cell wall. Schleiden had even supposed the nucleus to be a const.i.tuent part of the wall, sometimes lying enclosed between two layers of its substance, and Schwann quoted this view with seeming approval. Schwann believed, however, that in the mature cell the nucleus ceased to be functional and disappeared.

The main thesis as to the similarity of development of vegetable and animal tissues and the cellular nature of the ultimate const.i.tution of both was supported by a ma.s.s of carefully gathered evidence which a mult.i.tude of microscopists at once confirmed, so Schwann's work became a cla.s.sic almost from the moment of its publication. Of course various other workers at once disputed Schwann's claim to priority of discovery, in particular the English microscopist Valentin, who a.s.serted, not without some show of justice, that he was working closely along the same lines. Put so, for that matter, were numerous others, as Henle, Turpin, Du-mortier, Purkinje, and Muller, all of whom Schwann himself had quoted. Moreover, there were various physiologists who earlier than any of these had foreshadowed the cell theory--notably Kaspar Friedrich Wolff, towards the close of the previous century, and Trevira.n.u.s about 1807, But, as we have seen in so many other departments of science, it is one thing to foreshadow a discovery, it is quite another to give it full expression and make it germinal of other discoveries. And when Schwann put forward the explicit claim that "there is one universal principle of development for the elementary parts, of organisms, however different, and this principle is the formation of cells," he enunciated a doctrine which was for all practical purposes absolutely new and opened up a novel field for the microscopist to enter. A most important era in physiology dates from the publication of his book in 1839.

THE CELL THEORY ELABORATED

That Schwann should have gone to embryonic tissues for the establishment of his ideas was no doubt due very largely to the influence of the great Russian Karl Ernst von Baer, who about ten years earlier had published the first part of his celebrated work on embryology, and whose ideas were rapidly gaining ground, thanks largely to the advocacy of a few men, notably Johannes Muller, in Germany, and William B. Carpenter, in England, and to the fact that the improved microscope had made minute anatomy popular. Schwann's researches made it plain that the best field for the study of the animal cell is here, and a host of explorers entered the field. The result of their observations was, in the main, to confirm the claims of Schwann as to the universal prevalence of the cell. The long-current idea that animal tissues grow only as a sort of deposit from the blood-vessels was now discarded, and the fact of so-called plantlike growth of animal cells, for which Schwann contended, was universally accepted. Yet the full measure of the affinity between the two cla.s.ses of cells was not for some time generally apprehended.

Indeed, since the substance that composes the cell walls of plants is manifestly very different from the limiting membrane of the animal cell, it was natural, so long as the wall was considered the most essential part of the structure, that the divergence between the two cla.s.ses of cells should seem very p.r.o.nounced. And for a time this was the conception of the matter that was uniformly accepted. But as time went on many observers had their attention called to the peculiar characteristics of the contents of the cell, and were led to ask themselves whether these might not be more important than had been supposed. In particular, Dr. Hugo von Mohl, professor of botany in the University of Tubingen, in the course of his exhaustive studies of the vegetable cell, was impressed with the peculiar and characteristic appearance of the cell contents. He observed universally within the cell "an opaque, viscid fluid, having granules intermingled in it," which made up the main substance of the cell, and which particularly impressed him because under certain conditions it could be seen to be actively in motion, its parts separated into filamentous streams.

Von Mohl called attention to the fact that this motion of the cell contents had been observed as long ago as 1774 by Bonaventura Corti, and rediscovered in 1807 by Trevira.n.u.s, and that these observers had described the phenomenon under the "most unsuitable name of 'rotation of the cell sap.'" Von Mohl recognized that the streaming substance was something quite different from sap. He a.s.serted that the nucleus of the cell lies within this substance and not attached to the cell wall as Schleiden had contended. He saw, too, that the chlorophyl granules, and all other of the cell contents, are incorporated with the "opaque, viscid fluid," and in 1846 he had become so impressed with the importance of this universal cell substance that he gave it the name of protoplasm. Yet in so doing he had no intention of subordinating the cell wall. The fact that Payen, in 1844, had demonstrated that the cell walls of all vegetables, high or low, are composed largely of one substance, cellulose, tended to strengthen the position of the cell wall as the really essential structure, of which the protoplasmic contents were only subsidiary products.

Meantime, however, the students of animal histology were more and more impressed with the seeming preponderance of cell contents over cell walls in the tissues they studied. They, too, found the cell to be filled with a viscid, slimy fluid capable of motion. To this Dujardin gave the name of sarcode. Presently it came to be known, through the labors of Kolliker, Nageli, Bischoff, and various others, that there are numerous lower forms of animal life which seem to be composed of this sarcode, without any cell wall whatever. The same thing seemed to be true of certain cells of higher organisms, as the blood corpuscles.

Particularly in the case of cells that change their shape markedly, moving about in consequence of the streaming of their sarcode, did it seem certain that no cell wall is present, or that, if present, its role must be insignificant.

And so histologists came to question whether, after all, the cell contents rather than the enclosing wall must not be the really essential structure, and the weight of increasing observations finally left no escape from the conclusion that such is really the case. But attention being thus focalized on the cell contents, it was at once apparent that there is a far closer similarity between the ultimate particles of vegetables and those of animals than had been supposed. Cellulose and animal membrane being now regarded as more by-products, the way was clear for the recognition of the fact that vegetable protoplasm and animal sarcode are marvellously similar in appearance and general properties. The closer the observation the more striking seemed this similarity; and finally, about 1860, it was demonstrated by Heinrich de Bary and by Max Schultze that the two are to all intents and purposes identical. Even earlier Remak had reached a similar conclusion, and applied Von Mohl's word protoplasm to animal cell contents, and now this application soon became universal. Thenceforth this protoplasm was to a.s.sume the utmost importance in the physiological world, being recognized as the universal "physical basis of life," vegetable and animal alike. This amounted to the logical extension and culmination of Schwann's doctrine as to the similarity of development of the two animate kingdoms. Yet at the same time it was in effect the banishment of the cell that Schwann had defined. The word cell was retained, it is true, but it no longer signified a minute cavity. It now implied, as Schultze defined it, "a small ma.s.s of protoplasm endowed with the attributes of life." This definition was destined presently to meet with yet another modification, as we shall see; but the conception of the protoplasmic ma.s.s as the essential ultimate structure, which might or might not surround itself with a protective covering, was a permanent addition to physiological knowledge. The earlier idea had, in effect, declared the sh.e.l.l the most important part of the egg; this developed view a.s.signed to the yolk its true position.

In one other important regard the theory of Schleiden and Schwann now became modified. This referred to the origin of the cell. Schwann had regarded cell growth as a kind of crystallization, beginning with the deposit of a nucleus about a granule in the intercellular substance--the cytoblastema, as Schleiden called it. But Von Mohl, as early as 1835, had called attention to the formation of new vegetable cells through the division of a pre-existing cell. Ehrenberg, another high authority of the time, contended that no such division occurs, and the matter was still in dispute when Schleiden came forward with his discovery of so-called free cell-formation within the parent cell, and this for a long time diverted attention from the process of division which Von Mohl had described. All manner of schemes of cell-formation were put forward during the ensuing years by a mult.i.tude of observers, and gained currency notwithstanding Von Mohl's reiterated contention that there are really but two ways in which the formation of new cells takes place--namely, "first, through division of older cells; secondly, through the formation of secondary cells lying free in the cavity of a cell."

But gradually the researches of such accurate observers as Unger, Nageli, Kolliker, Reichart, and Remak tended to confirm the opinion of Von Mohl that cells spring only from cells, and finally Rudolf Virchow brought the matter to demonstration about 1860. His Omnis cellula e cellula became from that time one of the accepted data of physiology.

This was supplemented a little later by Fleming's Omnis nucleus e nucleo, when still more refined methods of observation had shown that the part of the cell which always first undergoes change preparatory to new cell-formation is the all-essential nucleus. Thus the nucleus was restored to the important position which Schwann and Schleiden had given it, but with greatly altered significance. Instead of being a structure generated de novo from non-cellular substance, and disappearing as soon as its function of cell-formation was accomplished, the nucleus was now known as the central and permanent feature of every cell, indestructible while the cell lives, itself the division-product of a pre-existing nucleus, and the parent, by division of its substance, of other generations of nuclei. The word cell received a final definition as "a small ma.s.s of protoplasm supplied with a nucleus."

In this widened and culminating general view of the cell theory it became clear that every animate organism, animal or vegetable, is but a cl.u.s.ter of nucleated cells, all of which, in each individual case, are the direct descendants of a single primordial cell of the ovum. In the developed individuals of higher organisms the successive generations of cells become marvellously diversified in form and in specific functions; there is a wonderful division of labor, special functions being chiefly relegated to definite groups of cells; but from first to last there is no function developed that is not present, in a primitive way, in every cell, however isolated; nor does the developed cell, however specialized, ever forget altogether any one of its primordial functions or capacities. All physiology, then, properly interpreted, becomes merely a study of cellular activities; and the development of the cell theory takes its place as the great central generalization in physiology of the nineteenth century. Something of the later developments of this theory we shall see in another connection.

ANIMAL CHEMISTRY

Just at the time when the microscope was opening up the paths that were to lead to the wonderful cell theory, another novel line of interrogation of the living organism was being put forward by a different set of observers. Two great schools of physiological chemistry had arisen--one under guidance of Liebig and Wohler, in Germany, the other dominated by the great French master Jean Baptiste Dumas. Liebig had at one time contemplated the study of medicine, and Dumas had achieved distinction in connection with Prevost, at Geneva, in the field of pure physiology before he turned his attention especially to chemistry. Both these masters, therefore, and Wohler as well, found absorbing interest in those phases of chemistry that have to do with the functions of living tissues; and it was largely through their efforts and the labors of their followers that the prevalent idea that vital processes are dominated by unique laws was discarded and physiology was brought within the recognized province of the chemist. So at about the time when the microscope had taught that the cell is the really essential structure of the living organism, the chemists had come to understand that every function of the organism is really the expression of a chemical change--that each cell is, in short, a miniature chemical laboratory. And it was this combined point of view of anatomist and chemist, this union of hitherto dissociated forces, that made possible the inroads into the unexplored fields of physiology that were effected towards the middle of the nineteenth century.

One of the first subjects reinvestigated and brought to proximal solution was the long-mooted question of the digestion of foods.

Spallanzani and Hunter had shown in the previous century that digestion is in some sort a solution of foods; but little advance was made upon their work until 1824, when Prout detected the presence of hydrochloric acid in the gastric juice. A decade later Sprott and Boyd detected the existence of peculiar glands in the gastric mucous membrane; and Cagniard la Tour and Schwann independently discovered that the really active principle of the gastric juice is a substance which was named pepsin, and which was shown by Schwann to be active in the presence of hydrochloric acid.

Almost coincidently, in 1836, it was discovered by Purkinje and Pappenheim that another organ than the stomach--namely, the pancreas--has a share in digestion, and in the course of the ensuing decade it came to be known, through the efforts of Eberle, Valentin, and Claude Bernard, that this organ is all-important in the digestion of starchy and fatty foods. It was found, too, that the liver and the intestinal glands have each an important share in the work of preparing foods for absorption, as also has the saliva--that, in short, a coalition of forces is necessary for the digestion of all ordinary foods taken into the stomach.

And the chemists soon discovered that in each one of the essential digestive juices there is at least one substance having certain resemblances to pepsin, though acting on different kinds of food. The point of resemblance between all these essential digestive agents is that each has the remarkable property of acting on relatively enormous quant.i.ties of the substance which it can digest without itself being destroyed or apparently even altered. In virtue of this strange property, pepsin and the allied substances were spoken of as ferments, but more recently it is customary to distinguish them from such organized ferments as yeast by designating them enzymes. The isolation of these enzymes, and an appreciation of their mode of action, mark a long step towards the solution of the riddle of digestion, but it must be added that we are still quite in the dark as to the real ultimate nature of their strange activity.

In a comprehensive view, the digestive organs, taken as a whole, are a gateway between the outside world and the more intimate cells of the organism. Another equally important gateway is furnished by the lungs, and here also there was much obscurity about the exact method of functioning at the time of the revival of physiological chemistry. That oxygen is consumed and carbonic acid given off during respiration the chemists of the age of Priestley and Lavoisier had indeed made clear, but the mistaken notion prevailed that it was in the lungs themselves that the important burning of fuel occurs, of which carbonic acid is a chief product. But now that attention had been called to the importance of the ultimate cell, this misconception could not long hold its ground, and as early as 1842 Liebig, in the course of his studies of animal heat, became convinced that it is not in the lungs, but in the ultimate tissues to which they are tributary, that the true consumption of fuel takes place. Reviving Lavoisier's idea, with modifications and additions, Liebig contended, and in the face of opposition finally demonstrated, that the source of animal heat is really the consumption of the fuel taken in through the stomach and the lungs. He showed that all the activities of life are really the product of energy liberated solely through destructive processes, amounting, broadly speaking, to combustion occurring in the ultimate cells of the organism. Here is his argument:

LIEBIG ON ANIMAL HEAT

"The oxygen taken into the system is taken out again in the same forms, whether in summer or in winter; hence we expire more carbon in cold weather, and when the barometer is high, than we do in warm weather; and we must consume more or less carbon in our food in the same proportion; in Sweden more than in Sicily; and in our more temperate climate a full eighth more in winter than in summer.

"Even when we consume equal weights of food in cold and warm countries, infinite wisdom has so arranged that the articles of food in different climates are most unequal in the proportion of carbon they contain. The fruits on which the natives of the South prefer to feed do not in the fresh state contain more than twelve per cent. of carbon, while the blubber and train-oil used by the inhabitants of the arctic regions contain from sixty-six to eighty per cent. of carbon.

"It is no difficult matter, in warm climates, to study moderation in eating, and men can bear hunger for a long time under the equator; but cold and hunger united very soon exhaust the body.

"The mutual action between the elements of the food and the oxygen conveyed by the circulation of the blood to every part of the body is the source of animal heat.

"All living creatures whose existence depends on the absorption of oxygen possess within themselves a source of heat independent of surrounding objects.

"This truth applies to all animals, and extends besides to the germination of seeds, to the flowering of plants, and to the maturation of fruits. It is only in those parts of the body to which arterial blood, and with it the oxygen absorbed in respiration, is conveyed that heat is produced. Hair, wool, or feathers do not possess an elevated temperature. This high temperature of the animal body, or, as it may be called, disengagement of heat, is uniformly and under all circ.u.mstances the result of the combination of combustible substance with oxygen.

"In whatever way carbon may combine with oxygen, the act of combination cannot take place without the disengagement of heat. It is a matter of indifference whether the combination takes place rapidly or slowly, at a high or at a low temperature; the amount of heat liberated is a constant quant.i.ty. The carbon of the food, which is converted into carbonic acid within the body, must give out exactly as much heat as if it had been directly burned in the air or in oxygen gas; the only difference is that the amount of heat produced is diffused over unequal times. In oxygen the combustion is more rapid and the heat more intense; in air it is slower, the temperature is not so high, but it continues longer.

"It is obvious that the amount of heat liberated must increase or diminish with the amount of oxygen introduced in equal times by respiration. Those animals which respire frequently, and consequently consume much oxygen, possess a higher temperature than others which, with a body of equal size to be heated, take into the system less oxygen. The temperature of a child (102 degrees) is higher than that of an adult (99.5 degrees). That of birds (104 to 105.4 degrees) is higher than that of quadrupeds (98.5 to 100.4 degrees), or than that of fishes or amphibia, whose proper temperature is from 3.7 to 2.6 degrees higher than that of the medium in which they live. All animals, strictly speaking, are warm-blooded; but in those only which possess lungs is the temperature of the body independent of the surrounding medium.

"The most trustworthy observations prove that in all climates, in the temperate zones as well as at the equator or the poles, the temperature of the body in man, and of what are commonly called warm-blooded animals, is invariably the same; yet how different are the circ.u.mstances in which they live.

"The animal body is a heated ma.s.s, which bears the same relation to surrounding objects as any other heated ma.s.s. It receives heat when the surrounding objects are hotter, it loses heat when they are colder than itself. We know that the rapidity of cooling increases with the difference between the heated body and that of the surrounding medium--that is, the colder the surrounding medium the shorter the time required for the cooling of the heated body. How unequal, then, must be the loss of heat of a man at Palermo, where the actual temperature is nearly equal to that of the body, and in the polar regions, where the external temperature is from 70 to 90 degrees lower.

"Yet notwithstanding this extremely unequal loss of heat, experience has shown that the blood of an inhabitant of the arctic circle has a temperature as high as that of the native of the South, who lives in so different a medium. This fact, when its true significance is perceived, proves that the heat given off to the surrounding medium is restored within the body with great rapidity. This compensation takes place more rapidly in winter than in summer, at the pole than at the equator.

"Now in different climates the quant.i.ty of oxygen introduced into the system of respiration, as has been already shown, varies according to the temperature of the external air; the quant.i.ty of inspired oxygen increases with the loss of heat by external cooling, and the quant.i.ty of carbon or hydrogen necessary to combine with this oxygen must be increased in like ratio. It is evident that the supply of heat lost by cooling is effected by the mutual action of the elements of the food and the inspired oxygen, which combine together. To make use of a familiar, but not on that account a less just ill.u.s.tration, the animal body acts, in this respect, as a furnace, which we supply with fuel. It signifies nothing what intermediate forms food may a.s.sume, what changes it may undergo in the body, the last change is uniformly the conversion of carbon into carbonic acid and of its hydrogen into water; the una.s.similated nitrogen of the food, along with the unburned or unoxidized carbon, is expelled in the excretions. In order to keep up in a furnace a constant temperature, we must vary the supply of fuel according to the external temperature--that is, according to the supply of oxygen.

"In the animal body the food is the fuel; with a proper supply of oxygen we obtain the heat given out during its oxidation or combustion."(3)

BLOOD CORPUSCLES, MUSCLES, AND GLANDS

Further researches showed that the carriers of oxygen, from the time of its absorption in the lungs till its liberation in the ultimate tissues, are the red corpuscles, whose function had been supposed to be the mechanical one of mixing of the blood. It transpired that the red corpuscles are composed chiefly of a substance which Kuhne first isolated in crystalline form in 1865, and which was named haemoglobin--a substance which has a marvellous affinity for oxygen, seizing on it eagerly at the lungs vet giving it up with equal readiness when coursing among the remote cells of the body. When freighted with oxygen it becomes oxyhaemoglobin and is red in color; when freed from its oxygen it takes a purple hue; hence the widely different appearance of arterial and venous blood, which so puzzled the early physiologists.

This proof of the vitally important role played by the red-blood corpuscles led, naturally, to renewed studies of these infinitesimal bodies. It was found that they may vary greatly in number at different periods in the life of the same individual, proving that they may be both developed and destroyed in the adult organism. Indeed, extended observations left no reason to doubt that the process of corpuscle formation and destruction may be a perfectly normal one--that, in short, every red-blood corpuscle runs its course and dies like any more elaborate organism. They are formed constantly in the red marrow of bones, and are destroyed in the liver, where they contribute to the formation of the coloring matter of the bile. Whether there are other seats of such manufacture and destruction of the corpuscles is not yet fully determined. Nor are histologists agreed as to whether the red-blood corpuscles themselves are to be regarded as true cells, or merely as fragments of cells budded out from a true cell for a special purpose; but in either case there is not the slightest doubt that the chief function of the red corpuscle is to carry oxygen.