Popular Science Monthly/Volume 49/September 1896/Some Modern Views of the Cell
By JAMES ELLIS HUMPHREY.
HARDLY more than a generation ago naturalists were forming, under the lead of the great Englishman, those conceptions of organic development and of the blood relationship of living beings resulting from common descent which have formed the starting point of almost all subsequent research. During the same years in which Mr. Darwin was accumulating the facts which were to form the imperishable foundations of his superstructure, various German investigators were gradually recording the observations that have afforded equally secure grounds for that view of the essential substance of living organisms which found expression at about the same time with the development theory, and which has exercised a hardly less profound influence upon biological investigation—the protoplasm theory.
But the beginnings of our knowledge of the intimate structure of plants and animals reach back two centuries further to the work of an English physicist and optician, Robert Hooke. This man, desiring to demonstrate his improvements in the manufacture of magnifying glasses, published in a volume entitled Micrographia, or some Physiological Descriptions of Minute Bodies made by Magnifying Glasses, in 1667, accounts of the appearance of various objects when viewed with his lenses. Among the objects upon which he had chanced was a piece of cork, and this he found to consist of a series of empty cavities separated by thin partitions, to which cavities he gave the name of cells, from their suggestion of the cells of a honeycomb. But although we now know that cork is a dead issue which no longer contains any essential component of the living cells, and although our conception of a cell is to-day quite opposed to that of a tightly closed chamber, such as the name implies, yet Hooke's name, given so long ago to the dead shell, is still retained for the living reality. And here we have one more example of the operation of that interesting conservatism of the human mind which perpetuates established terms or customs or beliefs long after their original fitness and raison d'étre have been outgrown.
Hooke's work was only one phase of the extraordinary scientific activity that characterized his time. The first fruit of the splendid awakening of the human mind from the paralysis of scholasticism which we owe to the Baconian philosophy was a zeal for the study of Nature; and from this period date some of the most brilliant discoveries in natural science. It is a notable coincidence that in the year 1671 there were presented to the lately established, but already famous Royal Society of London two elaborate treatises on the minute structure of plants, which had been quite independently worked out, the one by Grew, an Englishman, the other by Malpighi, an Italian. But their admi- rable work remained for more than a hundred years the standard of knowledge in plant anatomy, while the overwhelming author- ity and example of the Linnsean school reduced botany to the superficial examination of dried fragments, and comprised all needed knowledge of a plant in the determination of its Latin name.
For the beginnings of our real knowledge of the cell we must, then, leap the chasm of a century and a half to come again upon a period of improvement of the microscope as affording the means for further advance. In this case the important discoveries of Amici, resulting in lens systems in which both chromatic and spherical aberration were largely corrected, offered to histologists far better tools than had hitherto been at their command. Grew and Malpighi had distinguished in plants two kinds of elements, approximately isodiametric cells and much elongated vessels; but Treviranus had shown, early in the present century, that vessels are derived from rows of cells by the obliteration of intervening walls. And about the same time he had rediscovered the now familiar circulation in the gigantic cells of the brittleworts, or Characece, which, first described in 1772 by Corti, had been for- gotten in the zeal for taxonomy which possessed his contempo- raries. But gradually the idea grew that the contents within the walls of the cell are of importance; that the real cell is a living thing which nourishes itself and grows. One of the earliest clear expressions of this idea was written by Meyen in 1830, who spoke of cells of higher plants as "little plantlets in the greater." But the general spread of such views and general interest in cell prob- lems date from the time when Schleiden's clear mind was turned upon them. Going directly lo the heart of the whole matter as it then stood, he asked, "How do cells arise? " and set himself to answer the question. As a probable clew to its solution he seized, by a happy inspiration, upon the discovery made a few years before by Robert Brown that the cells of certain plants studied by him contained each a rounded, rather highly refractive body, which he had called, and which is still called, the nucleus. Demonstrating, with the aid of others, the very general occur- rence of this structure in plant cells, Schleiden made it the center of his theories of cell life and cell formation. It is true that his belief that new nuclei are formed by a sort of crystallization out of a mother-liquor and then form centers for the formation of new cells, has been proved to be incorrect. And it is equally true that his idea of the cell as a closed chamber filled with fluid, whose wall is its most essential part, is no longer entertained. Yet the fact that his theories turned attention to the cell contents also, and the fact that the most conspicuous object in almost any animal cell is its nucleus, made these most fruitful in their re- sults, as other mistaken theories have often been. The analogy between plant and animal cells, suggested by the presence of nuclei in both, led Schwann to thorough and profound investiga- tions of animal tissues, in which he happily recognized the funda- mental importance of the study of the development of a tissue for the elucidation of its nature. In this way he showed that animal tissues are made up of elementary units comparable with the cells of plants. The final recognition by Schleiden and Schwann, at the end of the fourth decade of the century, that all organisms consist wholly of cells and the products of their activity laid the solid foundations of the cell theory and brought animals and plants into new and most suggestive relations.
Studies of the nucleus had necessarily drawn attention to the granular substance which surrounds it and more or less com- pletely fills the cavity of the cell, and it had already been called "plant mucus "' by Schleiden. In 1844 Naegeli determined it to be a nitrogenous substance, and, together with von Mohl, recog- nized its presence in all living plant cells, while the latter bot- anist, two years later, first called it jjrotoplasm, or primitive substance. Up to this time the leading naturalists believed in impassable barriers and inherent differences between plants and animals. One of these supposed distinctions was the rigid and immotile character of plants as compared with the motile and contractile power of animals. The special contractile substance of animals, which was recognized as homogeneous or finely granular and albuminous, had already been called "sarcode" by Dujardin. But when, in 1850, Cohn showed that some plant cells possess no membrane and that their protoplasm shows the con- tractility and other supposedly characteristic properties of sar- code, he felt justified in saying with much certainty that "the protoplasm of the botanists and the contractile substance of the zoologists, if not identical, must yet be structures in a high degree analogous." But this conclusion, expressed incidentally in a paper on another subject, did not receive the attention it de- served. It was not until thirteen years later, when the way had been prepared by the work of De Bary on the Slime Molds and of Haeckel on the Radiolarians, that biologists were convinced by Max Schulze's masterly discussion of the subject of the identity of the substances in question. With the new view of the identity of all living substance went a radical change in the conception of the cell. The cell membrane, which is rarely present in animals, was relegated to the list of unessential constituents, and the vital center was transferred in mind to the cell contents, where it has been, in fact, since the beginning. The kernel of the new proto- plasm theory, which, as before stated, has since dominated research, is contained in Schulze's definition of a cell as "a lump of proto- plasm endowed with the properties of life," Yet for a few years some botanists found it difficult to give up the old idea of the active participation of the cell wall in the life of the cell, until Sachs's classic studies removed the last basis for such belief.
We have seen that Schleiden and Schwann recognized that it is only cells and their products which make up the substance of all organisms, but that their ideas of how cells arise were quite erroneous. It was soon observed by von Mohl and Naegeli that cells multiply by the division of those already present, and bota- nists soon came to the conclusion that plant cells can only come from previously existing ones. This conclusion was reached much more slowly for animals, since it presented many difficul- ties in the field of pathology, especially in connection with such processes as the formation of pus. But gradually the objections were shown to be of no weight, and the great pathologist Vir- chow, in 1858, gave expression to the result in the aphorism, "Om- nis cellula e cellula."
It will be noticed that the view of the cell current thirty years ago laid less stress upon the nucleus than that of twenty-five years earlier; and we shall see that more importance is attached to it to-day than ever before. Yet, so far as it went, Schulze's view of the nucleus was better than Schleiden's, for it recognized it as a specially differentiated organ of the protoplasm, though knowledge of its particular relations to the activity of the cell was very meager. Up to about 1875 it was generally thought by zoologists that, before the cell divides, the nucleus is constricted into two portions, one of which forms the nucleus of each of the new cells. The botanists, on the contrary, generally believed that the nucleus disappears before cell division, after which a new one appears in each new cell. These conclusions had been reached by studies of living dividing cells. Practically nothing had been done with preserved material, since no one trusted results so ob- tained or believed it possible to guard against artificial appear- ances due to the action of the preservative medium. The intro- duction of alcohol by Strasburger for killing and preserving tissues, and the proof by comparison with fresh material that no destructive or misleading changes are produced by it, mark the beginning of the epoch of cell studies, which has been charac- terized by a most astounding development of technical methods for killing, preserving, staining, and sectioning tissues of every sort with the least possible alteration in their living structure. The results of the first profound studies of the nucleus are con- tained in two volumes which laid the foundations for all future cell work—that of Strasburger on plant cells, which appeared in three editions from 1875 to 1880, and that of Flemming on animal cells, published in 1882. These authors showed that in both plants and animals cell division is ordinarily preceded by nuclear division. This latter process is not usually a mere constriction, but is, as we shall see, a highly remarkable and significant one, with a wonderful agreement in detail throughout both animal and vegetable kingdoms, so far as studied. The literature of the past fifteen years concerning this subject is of almost incredible volume, but it has all served to confirm the x>i'inie importance of the nucleus as an organ of the cell, and to show the correctness of Flemming's extension to the nucleus of the principle long before established for the cell, in writing "Omnis nucleus e nucleo."
While we attribute to the main mass of the protoplasm out- side of the nucleus less specialization than to the latter, there ap- pears to be a certain portion of it which has a special role. As early as 1883 the Belgian zoologist, Van Beneden observed that certain tiny protoplasmic masses bear a definite relation to nuclear division, and he expressed his belief that these should be regarded as definite organs of the cell. This view has steadily gained ground, and, although they were not recognized in plant cells until 1891, when Guignard discovered them, on account of their minute size and of the technical difficulties connected with mak- ing them visible, their general occurrence and importance may now be said to be well established. These tiniest of the known organs of the cell are called centrosplieres. Each consists of a central point surrounded by a mass of apparently homogeneous hyaline protoplasm.
Having now traced the development of our ideas, we are pre- pared to express our present conception of a typical cell as a mass of living protoplasm within which are difi:'erentiated a nucleus and one or two centrospheres. Many plants and ani- mals consist of single cells, while others are built up of mil- lions of these units of structure; but any organism is either an independent cell or an aggregation of cells more or less mutually interdependent. Some of the simplest unicellular organisms, like the Baderia, of whose work in the world we now hear so much, are so minute that no difi^erentiation within the cell has been observed. But rapid improvement in methods of study and means for observation are steadily reducing the number of these. Let us try, then, to get an idea of the best-established facts and views concerning the activities of the cell, and as to the part played by each of its organs in these activities.
Most plant cells are inclosed, as we have seen, in a firm wall, usually composed of a substance known as cellulose. Animal cells are, as a rule, without a definite membrane, and it is not certain that, in any case where a wall does exist, it consists of true cellulose.
The protoplasm of a cell is usually bounded at its outside by a denser hyaline layer which is very impermeable for fluids while living, and thus serves as a protection against the penetration of foreign or harmful substances into the cell. But this outer layer appears also to be the receptive x>ortion of the protoplasm which is sensitive to and transmits external stimuli. Within it is the rather fluid, undifilerentiated, granular protoplasm which consti- tutes the basis of the cell, and in which lie the special organs of which we have spoken. This wonderful mixture of albuminoid or proteid substances, which has well been called "the physical basis of life," must therefore possess those fundamental properties of living things, the power to assimilate, to grow, and to respond to external stimuli; and it is easy to show that living protoplasm possesses all these properties. But the one which most interests us just here is that of assimilation. This power of converting food into its own substance, which may result in the increase of that substance, or growth, seems specially to belong to the granu- lar protoplasm, which may be regarded as the nutritive organ of the cell. Just here we note that the food which may thus be assimilated must be organic substance. It may be proteid, like albumin, casein, or fibrin; it may be a carbohydrate, like sugar or starch; it may be a hydrocarbon, such as fat or oil; but or- ganic it must be. Whence comes now the supply of food? Plain- ly, in most cases, by absorption from without. In animals the solids and fluids taken in are reduced by digestion to the fluid form, and are then transported to the various cells of the organ- ism, to be absorbed and assimilated by them. In those plants known as fungi, which can develop only on living or dead organ- isms, the food materials are absorbed in fluid form, being some- times first reduced to that form by the action of a ferment secreted by the fungus. But certain cells of most plants have the power of manufacturing their own food from inorganic materials, and thus of living independently of other living things. Thus the green plants bridge over the chasm between the inorganic and the organic, and the life of all organized beings is practically con- tingent on their life. In the granular protoplasm of some cells of these plants may be found difl:erentiated protoplasmic masses which contain the green pigment cMorophyll, that gives them their color. First recognized early in the present century, these masses were observed by Naegeli, in 1S4G, to increase by division, and therefore to constitute living organs of the cells in which they occur. These chlorophyll bodies possess the synthetic power of recombining the elements of simple compounds obtained from the air and the soil, in the presence of light, into complex organic compounds which can serve the organism as food. Thus plant cells which contain chlorophyll bodies differ from all other cells in manufacturing their own food and in not being obliged to ob- tain it from without. Since in all or nearly all plants the lack of chlorophyll, when it is lacking, is due to degeneration in conse- quence of the acquirement of a saprophytic or parasitic mode of life, the possession of chlorophyll bodies and the consequent food- forming power constitute the most real distinction which sepa- rates plants from animals. Treated understandingly, this affords the most satisfying response to the ever-recurring demand for a statement of the differences between the two organic kingdoms, although the distinction is no more an absolute one, as shown by the case of the fvngi, than any of the other less important ones often suggested.
We have seen that most plant cells possess firm walls, and it is little more than a decade since plants were generally believed to consist of blocks of protoplasm quite shut off from each other, in most cases, by the surrounding walls. The many difficulties en- tailed by such belief, and the impossibility of explaining the transfer of substance or the transmission of stimuli in certain tissues, was the chief incentive to Gardiner's researches. This author and others after him have shown that, in most tissues, and especially just where they are needed to explain observed phe- nomena, tiny threads of protoplasm penetrate the cell walls, con- necting the protoplasmic masses of neighboring cells and forming the means of communication between them. So that we no longer think of the cells of a multicellular plant as isolated masses of protoplasm, but as connected masses, while the intervening walls give the necessary rigidity and resistance to the tissue.
Passing now to the nucleus of the cell, we find a complicated structure. Surrounded by undifferentiated protoplasm, it is bounded against it by a very delicate "nuclear membrane." With- in this is a loose network of somewhat solid substance, whose meshes are believed to be filled by a clear, structureless fluid. In this lie one or more small globular masses of a very strongly refractive substance, known as nucleoli. That the nucleus is the controlling organ in the more active cell processes is indicated by many facts. It has been found that a cell from which the nucleus has been removed is unable to grow or to form new cell wall. In cells in which growth or any active process is taking place at some definite point, the nucleus takes a position near to that point, although thus lying far from the center of the cell. Any shifting of the point of greatest activity is accompanied by a correspond- ing change in the position of the nucleus. The centrospheres lie ordinarily close beside the nucleus and play their chief role in connection with its division, which we may proceed to discuss. We have already seen how the conclusion was reached that cells can arise only from pre-existing cells, and that this occurs usually by division. Under favorable circumstances, when a growing cell has reached a certain rather indefinite limit of size, it proceeds to divide into two cells. But each of the new cells must have a nucleus and centrosphere; and we know that these can only arise from already existing ones, and by division. The process of nuclear division, as before remarked, is usually a very elaborate one, commonly known to students of the cell by the name karyokinesis. Indeed, so fundamentally important does this process appear, that the simpler method sometimes observed is believed by many biologists to have a pathological significance. The first sign of approaching karyokinetic division in a nucleus is the thickening of the threads of the nuclear network. This thickening continues, and at the same time the power of the threads to take up certain staining substances, now much used in their study, rapidly increases. Gradually the network resolves itself into a loose skein or coil, and at last this breaks up into a number, varying much in different species, but pretty constant in the same one, of separate rods or loops. These individualized portions of the original nuclear network have received the name of chromosomes, from their marked capacity for staining. Meanwhile the centrosphere, if previously single, has divided, and one of the pair has moved to each of the poles of the nucleus. At least in the higher plants, this division has occurred long before.
The nuclear membrane now disappears and there is formed, perhaps from the homogeneous protoplasm of the centrospheres, or from the substance of the nucleoli, or from both, a spindle-shaped framework of delicate fibers, about whose equator the chromosomes become arranged in a circle. Then is completed a process which may have begun much earlier, and each chromosome is split longitudinally into two. Of each pair of daughter chromosomes thus formed, one now passes toward one pole of the spindle and one toward the other. In the higher plants, each polar centrosphere divides into a pair at about the time of the splitting of the chromosomes. Thus finally there are accumulated at each pole as many daughter chromosomes as there were mother chromosomes formed in the mother nucleus. Each of the latter has furnished one of the former, as will be seen, to each group. The
chromosomes of each group now fuse by their ends into a thread, and this gradually thins out until, by an inverse process to that observed at the beginning of division, it passes into the condition of a nuclear network. Meantime new nuclear membranes have been formed and two daughter nuclei with accompanying centrospheres replace the original one. Just what the mechanics of karyokinesis is has not been determined with certainty; and students of the cell are not yet agreed whether the centrospheres exert an attractive influence on the chromosomes, or are mere passive points of attachment for the fibers of the spindle.
There remains one constituent of the nucleus whose fate during nuclear division has not been discussed. This is the substance which forms the nucleoli. These bodies usually disappear slowly while the chromosomes are becoming individualized, and very commonly have quite disappeared before the disappearance of the nuclear membrane. Nothing more is then seen of them until after the constitution of the daughter nuclei and the formation of their membranes. Then nucleoli reappear within these nuclei. To what parts of the cell their substance is distributed while they are unrecognizable, and what purpose they serve in the cell economy, we do not yet know; but they are probably composed of a reserve substance which furnishes material for some formative process, perhaps for the spindle fibers, as Strasburger now thinks. After the daughter nuclei are formed, the inclosing protoplasm divides between them, and thus there result two cells from the original one. In plants, their separation is commonly brought about by the formation of a distinct cellulose wall connecting with the original walls of the mother cell, and dividing the origi- nal compartment into two, and in most plants this wall begins to appear in the form of thickenings on the spindle fibers.
As we glance over this process of karyokinetic division just described, the phenomenon which must strike us as most signifi- cant is the longitudinal splitting of the chromosomes and the dis- tribution of the resulting halves. Why should this exact halving of each chromosome and the invariable contribution of one half to each new nucleus be necessary? If it were merely important to divide the substance of a nucleus about equally between the nuclei derived from it, no such painfully exact method would be necessary; and, if unnecessary, we can not believe it would have been developed. Yet it is common to animals and plants of the most varying complexity of structure, and therefore doubtless of profound significance. Let us reflect that the cells of a given plant or animal possess and perpetuate the characters of that species. In case of many organisms, all or most of their cells are capable, under certain conditions, of reproducing the species to which they belong. And a given cell is always true to its kind. In other words, any cell possesses the hereditary characters of its species, which it has received from its mother cell and which it transmits to its descendants to the last generation. Two cells from two dif- ferent organisms are, therefore, though indistinguishable in ap- pearance, really as different as the organisms from which they were taken. The transmission of hereditary characters from cell to cell must, then, be definitely provided for. A little considera- tion will show that the evidence points at present distinctly to the nucleus as the probable seat of those characters in the cell. And, of the different constituents of the nucleus, no other has so dis- tinct an individuality, or is so carefully divided between the daughter nuclei, as the substance of the chromosomes; while the evident need of a complete equipment of each nucleus with all the qualities of the species is quite met in its receiving an exact half of each chromosome. It is by no means proved, and it is perhaps not possible absolutely to prove, that the chromosomes are the material bearers of the hereditary characters of the species; but this view furnishes the best working hypothesis yet suggested as to the significance of the phenomena of karyokinosis. And it certainly correlates the concrete fact with the abstract problem in a most suggestive way.
In conclusion, it may be well to glance at some cell phenomena connected with reproduction. Allusion has already been made. incidentally, to vegetative or non-sexual reproduction, which pre- sents no further features of interest, since it differs from ordinary growth only in that the product of this form of growth does not usually remain attached to, and form a part of, the parent indi- vidual. On the contrary, it becomes separated, in most cases, from the parent, and sets out as a new individual. But in sexual reproduction we meet with a new complication. The phenomenon of sexual union, which occurs, at least occasionally, in an enor- mous majority of known organisms, and in very many must al- ways precede reproduction, is essentially a fusion of two cells. And, since the male cell often consists of little more than a nu- cleus, it may perhaps be reduced, in its final expression, to a fusion of two nuclei. Now it is observed that the number of chromo- somes in a dividing nucleus of a given species of plant or animal is approximately constant, and in the sexual nuclei quite so. After a male sexual nucleus containing, for example, twelve chromosomes has united with a female nucleus containing the same number, the fertilization nucleus thus produced proceeds to divide, and is seen to contain twenty-four chromosomes, or as many as were brought to it by both parent nuclei. And this number is found to persist without great variation in the nuclei of the new organism developed from the fertilized cell by success- ive divisions. It is plain that if the sexual elements produced from organisms of this generation contained twenty-four chromo- somes each, those of their sexually produced offspring would have forty-eight each, and the point would soon be reached by success- ive doublings at which the capacity of the nucleus would be far overtaxed by the number of chromosomes. But this diflSculty is avoided, in the plants and animals thus far investigated, by an abrupt reduction to one half the number usual in the organism, of the chromosomes of the nuclei of certain cells which are to give rise to the sexual cells. This reduced number remains constant in all the descendants of the nuclei in which it first appears, until the definitive sexual cells are formed. Then the fusion of two nuclei, each with the half number of chromosomes, restores to the resulting organism the typical number. This reduction has been spoken of as abrupt; and it could not well be more so. A nucleus in which it occurs receives from its mother nucleus, let us say, twenty-four chromosomes which fuse together to form its nuclear network. When, after a period of rest, this nucleus proceeds to divide, it develops from its network but twelve chromosomes, and therefore furnishes but twelve to each of its daughter nuclei. What has become of the other twelve no one can say, because nothing is known of the exact relations that exist between the in- dividual chromosome of the dividing nucleus and any part of the network of the resting stage. It is probable that this remarkable process of reduction has some far-reaching significance with reference to the origin and meaning of sexuality. Already theories concerning it have been suggested; but we are yet on the threshold of knowledge of the facts on which profitable theories must be based, and, until we have penetrated further within the portal, we can afford to suppress our propensity for speculation.