Form and Function Part 18

Theodor Schwann was a pupil of Johannes Muller, and we know that Muller took much interest in the new histology. It is probably to his influence that we owe Schwann's brilliant work on the cell, which appeared just after Schwann left Berlin for Lowen. Schwann was himself, as his later work showed, more a physiologist than a morphologist; he did quite fundamental work on enzymes, discovering and isolating the pepsin of the gastric juice; he proved that yeast was not an inorganic precipitate but a ma.s.s of living cells; he carried out experiments directed to show that spontaneous generation does not occur. We shall see in his treatment of the cell-theory clear indications of his physiological turn of mind.

Schwann was only twenty-nine when his master-work appeared, and the book is clearly the work of a young man. It has the clear structure, the logical finish, which the energy of youth imparts to its chosen work. So the work of Rathke's prime, the _Anatomische-philosophische Untersuchungen_ of 1832 shows more vigour and a more reasoned structure than his later papers. Schwann's book is indeed a model of construction and c.u.mulative argument, and even for this reason alone justly deserves to rank as a cla.s.sic.

The first section of his book is devoted to a detailed study of the structure and development of cartilage cells and of the cells of the notochord, and to a comparison of these with plant cells. He accepts Schleiden's account of the origin and development of nuclei and cells as a standard of comparison; and he seeks to show that nucleus and nucleolus, cell-wall and cell-contents, show the same relations and behave in the same manner in these two types of animal cells as in the plant-cells studied by Schleiden. The types of cell which he chose for this comparison are the most plant-like of all animal cells, and he was even able to point to a thickening of the cell-wall in certain cartilage cells, a.n.a.logous to the thickening which plays so important a part in the outward modification of plant-cells. The a.n.a.logy indeed in structure and development between chorda and cartilage cells and the cells of plants seemed to him complete. The substance of the notochord consisted of polyhedral cells having attached to their wall an oval disc similar in all respects to the nucleus of the plant-cell, and like it containing one or more nucleoli. Inside the mother-cell were to be found young developing cells of spherical shape, lacking however a nucleus.

Cartilage was even more like plant tissue. It was composed of cells, each with its cell membrane. The cells lay close to one another, separated only by their thickened cell-wall and the intercellular matrix, showing thus even the general appearance of the cellular tissue of plants. They contained a nucleus with one or two nucleoli, and the nucleus was often resorbed, as in plants, when the cell reached its full development. Other nuclei were in many cases present in the cell, round which young cells could be seen to develop, in exactly the same manner as in plants. These nuclei had accordingly the same significance as the nuclei of plants, and deserved the same name of cytoblasts or cell-generators. The true nucleus of the cartilage cell was probably in the same way the original generator of the mother-cell.

Having proved the ident.i.ty in structure and function of the cells of these selected tissues with the cells of plants, as conceived by Schleiden, Schwann had still to show that the generality of animal tissues consisted either in their adult or in their embryonic state of similar cells. This demonstration occupies the second and longest section of his book.

His method is throughout genetic; he seeks to show, not so much that all animal tissues are actually in their finished state composed of cells and modifications of cells, as that all tissues, even the most complex, are developed from cells a.n.a.logous in structure and growth with the cells of plants.

All animals develop from an ovum; it was his first task to discover whether the ovum was or was not a cell. It happened that, some years before Schwann wrote, a good deal of work had been done on the minute structure of the ovum, particularly by Purkinje and von Baer. Purkinje in 1825[252] discovered and described in the unfertilised egg of the fowl a small vesicle containing granular matter, which he named the _Keimblaschen_ or germinal vesicle. It disappeared in the fertilised egg. As early as 1791 Poli had seen the germinal vesicle in the eggs of molluscs, but the first adequate account was given by Purkinje. In 1827[253] von Baer discovered the true ova of mammals and cleared up a point which had been a stumbling block ever since the days of von Graaf, who had described as the ova the follicles now bearing his name.[254] Even von Graaf had noticed that the early uterine eggs were smaller than the supposed ovarian eggs; Prevost and Dumas[255] had observed the presence in the Graafian follicle of a minute spherical body, which, however, they hesitated to call the ovum; it was left to von Baer to elucidate the structure of the follicle and to prove that this small sphere was indeed the mammalian ovum. His discovery was confirmed by Sharpey and by Allen Thomson. Von Baer found the germinal vesicle in the eggs of frogs, snakes, molluscs, and worms, but not in the mammalian ovum; he considered the whole mammalian ovum to be the equivalent of the germinal vesicle of birds--a comparison rightly questioned by Purkinje (1834). In 1834 Coste[256] discovered in the ovum of the rabbit a vesicle which he considered to be the germinal vesicle of Purkinje; he observed that it disappeared after fertilisation. Independently of Coste, and very little time after him, Wharton Jones[257] found the germinal vesicle in the mammalian ovum. Valentin in 1835,[258] Wagner in 1836,[259] and Krause in 1837,[260] added considerably to the existing knowledge of the structure of the ovum. Wagner in his _Prodromus_ called attention to the widespread occurrence, within the germinal vesicle of a darker speck which he called the _Keimfleck_ or germinal spot, known sometimes as Wagner's spot. He recognised the _Keimfleck_ in the ova of many cla.s.ses of animals from mammals to polyps. Frequently more than one _Keimfleck_ occurred.

Schwann had therefore a good deal of exact knowledge to go upon in discussing the significance of the ovum for the cell-theory. There were two possible interpretations. Either the ovum was a cell and the germinal vesicle its nucleus, or else the germinal vesicle was itself a cell within the larger cell of the ovum and the germinal spot was its nucleus. Schwann had some difficulty in deciding which of these views to adopt, but he finally inclined to the view that the ovum is a cell and the germinal vesicle its nucleus, basing his opinion largely upon observations by Wagner which tended to prove that the germinal vesicle was formed first and the ovum subsequently formed round it. But the ovum was not, in Schwann's view, a simple cell, for within it were contained yolk-granules, one set apparently containing a nucleus, the others not.

Even the second set, those composing the yellow yolk, were considered by Schwann to deserve the name of cells, because, although a nucleus could not be observed in them, they had a definite membrane, distinct from their contents--a conception of the cell obviously dating from the earliest botanical notions of cells as little sacs. The yolk cells were not mere dead food material but living units which took part in the subsequent development of the egg. The relation between the unfertilised egg and the blastoderm which arises from it is not made altogether clear by Schwann. According to his account the cells of the blastoderm are formed actually in the ovum. Round the nucleus of the egg appears a _Niederschlag_ or precipitate which is the rudiment of the blastoderm (p. 68). When the egg leaves the ovary the nucleus disappears, leaving behind it this rudiment of the blastoderm, which rapidly grows and increases in size. The blastoderm of the chick before incubation is found to be composed of spherical anucleate bodies which Schwann considers to be cells, because they almost certainly develop into the cells of the incubated blastoderm, which are clearly recognisable as such after eight hours' incubation. The serous and mucous layers can be distinguished after sixteen hours' incubation, and it is found that the cells of the serous layer contain definite nuclei, though such seem to be absent in the cells of the mucous layer. Between the two layers other cells are formed belonging to the vessel layer, which is, however, in Schwann's opinion not a very definitely individualised layer.

Schwann's next step is a detailed demonstration of the origin of each tissue from simple cells such as those composing the incubated blastoderm.

"The foregoing investigation has taught us that the whole ovum shows nothing but a continual formation and differentiation of cells, from the moment of its appearance up to the time when, through the development of the serous and mucous layers of the blastoderm, the foundation is given for all the tissues subsequently appearing: we have found this common parent of all tissues itself to consist of cells; our next task must be to demonstrate not only in this general way that tissues originate from cells, but also that the special formative ma.s.s of each tissue is composed of cells, and that all tissues are either const.i.tuted by simple cells or by one or other of the manifold kinds of modified cells" (p.

71). Five cla.s.ses of tissue can be distinguished, according to the extent and manner of the modifications which the cells composing them have undergone. There are first of all independent and isolated cells, such as the corpuscles of the blood and lymph, not forming a coherent tissue in the ordinary sense. Next there are the a.s.semblages of cells lying in contiguity with one another, but not in any way fused; examples of this cla.s.s are the epidermal tissues and the lens of the eye. In the third cla.s.s come tissues the cells of which have fused by their walls, but whose cell-cavities are not in continuity, such as osseous tissue and cartilage. In the tissues of the fourth cla.s.s, comprising the most highly specialised of all, not only are the cell-walls continuous but also the cell-cavities; to this cla.s.s belong muscle, nerve and capillary vessels. A fifth cla.s.s, of rather a special nature, includes the fibrous tissues of all kinds. This is the first cla.s.sification of tissues upon a cellular basis, and it marks the foundation of a new histology which took the place of the "general anatomy" of b.i.+.c.hat. The exhaustive account which Schwann gives of the structure and development of the tissues in this section of his book const.i.tutes the first systematic treatise on histology in the modern sense, and it is still worth reading, in spite of many errors in detail.

Schwann found it easy to demonstrate the cellular nature of the tissues of his first three cla.s.ses. With the other two cla.s.ses he had more difficulty. Fibres of all kinds, he considered, arose by an elongation of cells, which afterwards split longitudinally into long strips, forming as the case might be white or elastic fibrous tissue.

Muscle-fibres and nerve-fibres were formed in a totally different way, by coalescence of cells; each separate muscle-fibre and nerve-fibre was thus a compound cell. Capillaries, Schwann held, were formed by cells hollowed out like drain-pipes, and set end to end--a mistaken view soon corrected by Vogt (_Embryologie des Salmones_, p. 206, 1842).

In this detail part of his book Schwann acc.u.mulates material for a general theory of the cell which he develops in the third and last section. Taking up the physiological or dynamical standpoint, he points out that one process is common to all growth and development of tissues both in animals and plants, namely, the formation of cells, a process which he conceives to take place in the following manner. There is, first of all, a structureless substance, the cytoblastem, the matrix in which all cells originate. The cytoblastem may be either inside the cells, or, more usually, in the s.p.a.ces between them. It is not a substance of definite chemical and physical properties, for the matrix of cartilage and the plasma of the blood alike come within the definition. It has largely the significance of food material for the developing cells. In plants, according to Schleiden, cells are never formed in the intercellular substance--the cytoblastem is within the cells; but extracellular cell formation seems to be the general rule in animals. An intracellular formation of cells occurs only in the ovum, in cartilage cells and chorda cells and in a few others, and even there it is not the exclusive method of formation; a formation of cells within cells never occurs in muscles and nerves, nor in fibrous tissue (p.

204). In the cytoblastem granules appear, which gradually increase in size and take on the characteristic shape of nuclei; round each of these a young cell is formed. Sometimes the young cells appear to have no nuclei, as in the intracellular brood of chorda cells, but, as a rule, a nucleus is clearly visible. The nucleus is indeed the most characteristic const.i.tuent of the cell. "The most important and most constant criterion of the existence of a cell is the presence or absence of the nucleus," writes Schwann near the beginning of his book (p. 43).

As a general rule the nucleolus is formed first, and round it by a sort of condensation or concretion the nucleus, which is frequently hollow, and round this again, by a somewhat similar process, the cell. "The whole process of the formation of a cell consists in the precipitation round a small previously formed corpuscle (the nucleolus) of first one layer (the nucleus) and then later round this a second layer (the cell substance)" (p. 213). The outermost layer of the cell usually thickens to form the membrane, but this membrane formation does not always occur, and the membrane is not present in all cells. The nucleus is formed in exactly the same manner as the cell, and it might with much truth itself be called a cell--a cell of the first order, while ordinary nucleated cells might be designated cells of the second order (p. 212). In anucleate cells there is probably only a single process of layer formation round an infinitely small nucleolus. In almost all nucleate cells the nucleus is resorbed when the cell reaches its full development, and it is larger and more important the younger the cell is.

The cell was for Schwann not a morphological concept at all, but a physiological; the cell was a dynamical, not a statical unit.

Cell-formation was the process at the back of all production of life, and cells were the centres of all vital activity. Each cell was itself an organism, and its life and activities were to some extent independent of the lives and activities of all the other cells. The multicellular organism was a colony of unicellular organisms, and its life was a sum of the lives of its const.i.tuent elements. This "theory of the organism,"

which holds so important a place in biology even at the present day, is developed by Schwann in the concluding pages of his book.

He begins by contrasting the teleological with the materialistic conception of living things. In the teleological view, a special force works in the living organism, guiding and directing its activities towards a purposeful end. According to the materialistic view there are no other forces at work in the living organism than those which act in the inorganic realm, or at least there are none but forces at one with these in their blindness and necessity. True, the purposiveness of living processes cannot be denied; but its ground lies, according to this view, not in a vital force which guides and rules the individual life, but in the original creation and collocation of matter according to a rational plan. The purposiveness of life is part of the purposiveness of the universe; just as the stars circle for ever in harmoniously adjusted paths, so do the processes of life work together towards a common end. Both are the inevitable result of the original distribution of matter in the primitive chaos, a distribution fixed by a rational and foreknowing Being (p. 222).

Which of the two conceptions is to be adopted in biology? Teleological explanations have long been banished from the physical sciences, and in biology they are only a last resort when physical explanations have proved incomplete (p. 223). And if the ground of the purposiveness of living Nature is the same as the ground of the purposiveness of the universe, is it not reasonable to suppose that explanations which have proved satisfactory for inorganic things will in time with sufficient knowledge prove adequate also for organic things?

The teleological conception, again, leads to difficulties particularly when it is applied to the facts of reproduction. If we suppose that a vital force unifies and coordinates the organism and is its very essence, we must also suppose that this force is divisible and that a part of it--separated in reproduction--can bring about the same results as the whole. If on the contrary the forces having play in the organism are the mere result of the particular combination of the matter composing it, the reconstruction of a particular combination of molecules in the ovum is all that is necessary to set development a-going along exactly the course taken by the ovum of the parent.

Another argument against the teleological view is derived from the facts of the cell-theory. The cell-theory tells us that the molecules of the living body are not immediately built up in manifold combinations to form the organism, but are formed first into unit-constructions or cells, and that these units of composition are invariably formed in all development, of plants and animals alike, however diverse the goal of development may be. If there were a vital principle would we not expect to find that, scorning this roundabout way of reaching its goal, it went straight to the mark, taking a different and distinctive course for each individual development, building up the organism direct without the intermediary of cells? But since there is a universal principle of development, namely, the formation of cells, does it not seem that the cells must be the true organisms, that the whole "individual" organism must be an aggregate of cells, and that the concept of individuality applied to the organism is accordingly a logical fiction? And it is just upon this notion of the individuality of the organism that the teleological concept is based. The teleological view can perhaps not be completely refuted until the adequacy of materialistic explanations has been finally shown; but it is certain that the most promising method for research is the materialistic (p. 226).

"We start out then from the a.s.sumption that the basis of the organism is not a force acting according to a definite plan; on the contrary, the organism arises through the action of blind and necessary laws, of forces which are as much implicit in matter as those of the inorganic world. Since the chemical elements in organic Nature differ in no way from those of inorganic Nature, the ground or cause of organic phenomena can consist only in a different mode of combination of matter, either in a peculiar mode of combination of the elementary atoms to form atoms of the second order, or in the particular arrangement of these compound molecules to form the separate morphological units of the organism or the whole organism itself" (p. 226). Accepting then the materialistic conception of the organism, we have to consider this further problem.

Does the ground of organic processes lie in the whole organism or in its elementary parts? Translated into terms of metabolism--note the physiological point of view--the question runs, are metabolic processes the result of the molecular construction of the organism as a whole, or does the centre of metabolic activity lie in the cell? Is it the cell rather than the organism that is the immediate agent of a.s.similatory processes? In the first alternative the cause of the growth of the const.i.tuent parts lies in the totality of the organism; in the other alternative:--"Growth is not the result of a force having its ground in the organism as a whole, but each of the elementary parts possesses a force of its own, a life of its own, if you will; that is to say, in each elementary part the molecules are so combined as to set free a force whereby the cell is enabled to attract new molecules and so to grow, and the whole organism exists only through the reciprocal action of the single elementary parts.... In this eventuality it is the elementary parts that form the active element in nutrition, and the totality of the organism can be indeed a condition, but on this view it cannot be a cause" (p. 227).

To help in the decision of this question, appeal must be made to the facts established as to the cellular nature of the organism and of its reproductive elements. We know that every organism is composed of cells, which are formed and grow according to the same laws wherever they are found, whose formation therefore is everywhere due to the same forces.

If we find that certain of these cells--all of which we know to be essentially identical one with another--have the power when separated from the others of growing and developing into new organisms, we can infer that not only such cells but also all other cells have this a.s.similatory power. The ova of animals, the spores of plants, the isolated cells of lower organisms in general, all show the power of separate a.s.similation and development. "We must therefore, in general, ascribe to the cell an individual life, that is to say, the combination of the molecules in the single cell does suffice to produce the force whereby the cell is enabled to draw to itself new molecules. The ground of nutrition and growth lies not in the organism as a whole, but in the separate elementary parts, the cells. The fact that it is not every cell that can continue to grow when separated from the organism is not in itself an objection to this theory, any more than it is an objection to the individual life of a bee that it cannot continue to exist apart from the swarm. The activation of the forces existing within the cell depends on conditions which the cell encounters only in connection with the whole" (pp. 228-9).

Schwann's next step is to discover what are the essential forces active in the cell, and here he enters the realm of hypothesis. He finds they can be reduced to two--an attractive force and a metabolic force. The attractive force is seen in the process of cell-formation, where first of all the nucleolus is formed by a concentration and precipitation of substances found free in the cytoblastem, and in the same way the nucleus and later the cell are laid down as concentric precipitates from the cytoblastem. Cell-formation also involves the second or metabolic force, by means of which the cell alters the chemical composition of the medium surrounding it so as to prepare it for a.s.similation. Schwann's attractive force brings about the actual taking up of the prepared substance; his metabolic force is the cause of the digestion of food substances, and is nearly identical with enzyme action. With what inorganic process, he now asks (p. 239), can the process of cell-formation be most nearly compared, and the answer obviously is, with the process of crystallisation. Cells are, it is true, quite different in shape and consistency from crystals, and they grow by intussusception, not by apposition--their plastic or attractive forces seem therefore to be different. A still more important difference is that the metabolic force is peculiar to the cell. Yet there are important a.n.a.logies between crystals and cells. They agree in the important respect that they both grow in solutions at the cost of the dissolved substance, according to definite laws, and develop a definite and characteristic shape. It might even be maintained, Schwann thinks, that the attractive force of crystals is really identical with that of cells, and that the difference in result is due merely to the difference between the substance of the cell and the substance of the crystal. He points out how organic bodies are remarkable for their powers of imbibition, and he seeks to show that the cell is the form under which a body capable of imbibition must necessarily crystallise, and that the organism is an aggregate of such imbibition-crystals. The a.n.a.logy between crystallisation and cell-formation he works out in the following manner:--"The substance of which cells are composed possesses the power of chemically transforming the substance with which it is in immediate contact, in somewhat the same way as the well-known preparation of platinum changes alcohol into acetic acid. Each part of the cell possesses this property. If now the cytoblastem is altered by an already formed cell in such a way that a substance is formed that cannot become part of the cell, it crystallises out first as the nucleolus of a new cell. This in its turn alters the composition of the cytoblastem. A part of the transfomed substance may remain in solution in the cytoblastem or may crystallise out as the beginning of a new cell; another part, the cell-substance, crystallises round the nucleolus. The cell-substance is either soluble in the cytoblastem and crystallises out only when the latter is saturated with it, or it is insoluble and crystallises as soon as it is formed, according to the aforementioned laws of the crystallisation of imbibition-bodies; it forms thus one or more layers round the nucleolus, etc. If one imagines cell-formation to take place in this way, one is led to think of the plastic force of the cell as identical with the force by means of which a crystal grows" (pp.

249-50).

Two difficulties have to be faced by this theory--(1) the origin of the metabolic power of the cells, (2) the reason why the cells arrange themselves so as to form an organism of complex and definite structure.

Schwann tries to explain the origin of the "metabolic" action, the a.n.a.logy of which with the contact-action of colloidal platinum he recognises, by attributing it to the peculiar structural arrangements of molecules. In attempting to account for the harmonious structure of the organism he points to the a.n.a.logy of ordinary crystals, which often form complex and regular tree-like arrangements; plants in particular resemble these regularly shaped crystal-aggregates.

The whole ingenious theory is offered merely as an hypothesis and a guide to research. It is interesting as one of the most carefully thought-out attempts ever made to give a thorough-going materialistic account of the origin and development of organic form, and it arose directly out of the cell-theory.

Schleiden and Schwann started out from an erroneous theory of the origin and development of cells, which impaired to some extent the value of their results. It was not long, however, before their theory of the origin of cells by "crystallisation" from an intra- or extra-cellular cytoblastem was challenged and overthrown, and the generalisation that cells originate by division from pre-existing cells put in its place.

This was established for plant cells by Meyen, Unger, von Mohl, Naegeli and Hofmeister in or about the forties.[261] Criticism of the Schwann-Schleiden theory from the zoological side was suggested by the study of the segmentation of the ovum--the developmental process in which the multiplication of cells is most easily observed. The segmentation of the ovum was well known to Schwann, for the process had been described in the frog by Prevost and Dumas in 1824,[262] in the frog and newt by Rusconi,[263] and an elaborate study of the process in the frog had been made by von Baer.[264] Schwann indeed suspected that there must be some connection between the segmentation of the ovum and the formation of cells, but he did not realise that the cellular blastoderm of the chick was formed by the division or segmentation of the egg-cell.

Segmentation was soon found to be of widespread occurrence. Von Siebold in 1837 described the process in Entozoa,[265] and in the same year Loven saw segmentation in _Campanularia_,[266] and Sars in the starfish and in Nudibranchs.[267]

In 1838 Bischoff[268] observed segmentation in the mammalian ovum, and the whole course of segmentation in the ovum of the rabbit from the 2-celled to the morula stage was carefully described and figured by Barry[269] in 1839. C. Vogt[270] in 1842 described segmentation in _Coregonus_ and _Alytes_. The discovery of segmentation in the ovum of birds was not made until 1847, by Bergmann,[271] confirmed independently by Coste[272]

in 1850. By 1848 segmentation had been noted in _Hydra_ and various hydroids, in acalephs, in starfish, polyzoa, nematodes, rotifers, leeches, oligochaetes, polychaetes, in most groups of molluscs and arthropods, and in all the vertebrate cla.s.ses.[273]

The process was at first held to be merely one of yolk-division, or _Dotterfurchung_, and its details were by most interpreted in the light of the Schleiden-Schwann theory of cell-formation.

The first steps towards a truer conception of the process seem to have been taken by Bergmann, who in 1841[274] called attention to the presence of nuclei in the segmentation-spheres of the frog's egg, and by Bagge in the same year, who observed that division of the nuclei preceded the multiplication of the segmentation spheres.[275] He considered the nuclei to be anucleate cells, and the same view was taken by Kolliker in 1843.[276] Next year, however, in his cla.s.sical paper on Cephalopod development[277] Kolliker came to the opinion that they were really nuclei. He showed that segmentation was brought about by cell-division, that between "total" and "partial" segmentation there was a difference of degree and not of kind, and that the cells of the body were formed by division of the segmentation spheres. He held, however, that the nuclei multiplied endogenously and not by division. The division of nuclei was observed by Coste in 1846.[278] Leydig in 1848[279] took the necessary step in advance and maintained that the nuclei as well as the cells increased always by division. He was supported by Remak, who in a paper of 1852,[280] and more fully in his monumental _Untersuchungen uber die Entwickelung der Wirbelthiere_ (Berlin, 1850-55), proved that in the frog's egg at least segmentation was a simple process of cell-division, initiated always by division of the nucleus.[281]

One point Remak left undecided--the fate of the _Keimblaschen_ or egg-nucleus. It was generally held, even so late as the 'fifties, that the egg-nucleus disappeared just before segmentation began--Bischoff clung to this belief even in 1877.[282] Though Barry had held in 1839 that the egg-nucleus does not disappear in segmentation, J. Muller seems to have been the first actually to prove that it forms by division the nuclei of the first two segmentation spheres. He furnished the demonstration in the egg of _Entoconcha mirabilis_,[283] and his paper was known to Remak, who could not, however, observe a similar division of the egg-nucleus in the frog. Muller's discovery was confirmed for _Oceania armata_ by Gegenbaur,[284] and for _Notommata sieboldii_ by Leydig.[285]

In 1854 Virchow,[286] previously a supporter of Schwann, crystallised the new views in the famous phrase--_Omnis cellula e cellula_--and gave wide publicity to them in his cla.s.sical lectures on Cellular Pathology, delivered in 1858.[287] The new doctrine of cell-formation was also taught by Leydig[7] in his text-book of histology, published in 1857.

The Schleiden-Schwann theory of the origin of cells by generation in a cytoblastem was now definitely overthrown.

The importance of the protoplasmic content of the cell was brought into prominence through the work of Dujardin,[289] Purkinje,[290] Cohen[291] and Max Schultze.[292] The last-named in 1861 proposed a definition of the cell which might be accepted at the present day. "A cell," he wrote, "is a little blob of protoplasm containing a nucleus" (p. 11).

[238] _Theoria generationis_, Halae, 1759.

[239] See J. v. Sachs, _Geschichte der Botanik_, book ii., Eng. Trans., 2nd impr., 1906.

[240] Muller's _Archiv_, pp. 137-76, 1838.

[241] _Trans. Linnean Soc._, xvi., p. 710, 1833.

[242] _Myxinoiden_, i. Theil., p. 89, 1835.

[243] _Ann. Sci. nat._ (2) (_Zool._) ii., pp. 107-18, pl.

11, 1834.

[244] _Proc. Phil. Soc. Glasgow_, xix., pp. 71-125, 1887-8.

[245] _Traite sur le venin de la vipere_, 1781.

[246] Muller's _Archiv_, 1836.

[247] J. Muller, _Jahresbericht u. d. Fortschritte der anat.-physiol. Wissenschaften im Jahre_ 1838. Muller's _Archiv_, 1838.

[248] _Symbolae ad anatomiam villorum imprimis eorum epithelii_, Berlin, 1837.

[249] _U. d. Ausbreitung des Epitheliums im menschlichen Korper_. Muller's _Archiv_, 1838.

[250] See Schwann's _Bemerkungen_ at the end of his _Mikroskopische Untersuchungen_.