The History of Biological Theories

Plant cells consist as a rule of the following parts: Firstly, a tough membrane, the cell-wall, which consists of a substance chemically related to starch. Secondly and within this, a colourless, semi-fluid substance the protoplasm. This lines the wall, and stretches out as threads which unite it with a denser mass of the same substance the nucleus. Thirdly, vacuoles, filled with a watery fluid containing various substances in solution. The protoplasm is a colourless, homogeneous ground substance, containing numerous very small bodies the microsomes.

Plant protoplasm often contains larger bodies leuco- plasts which form starch, and green chlorophyll bodies chloroplasts to which the green colour of the plant is due. Plant protoplasm appears to be in continual motion while alive. It always contains a nucleus, generally oval in shape, which is in its turn made up of various com- ponents. One of these can be easily stained and is called chromatin. The living cell absorbs the raw materials and energy which it needs, and produces the substances upon which it lives ; it can grow, and, when free, can change its shape ; it is irritable, and can reproduce itself.

The phenomena accompanying cell division have been much studied. Since Virchow's time it has been generally admitted that new cells can only be formed by the division of pre-existing ones. The chromatin of the nucleus at first collects into chromatin granules these group them- selves as threads, and these then collect into a ball. At each of the two 'poles' of the nucleus a small body appears the centrosome ; the two centrosomes mark the points where the new nuclei which will arise from the old one will appear. The threads of the ball now look like horse- shoe-shaped loops (chromosomes); these are grouped in the equatorial plane midway between the two centro- somes. The chromosomes can now be counted, and each type of animal and plant possesses a definite number of chromosomes. 1 The smallest number known is two yet 168 or even more occur in some cases. The relation, if there is any, between the number of chromosomes and the other characteristics of an organism, is quite unknown.

Each chromosome now divides lengthways into two; one half moves towards the one centrosome, the other towards the other. All the chromosomes at each pole collect and form a tangled lump in this position. Then they return to the state of chromatin granules, and so finally form a new nucleus. Meanwhile the protoplasm itself also divides by simple constriction into two parts, and so, from the 'mother' cell, two 'daughter' cells arise. They may separate and live as single cells (in unicellular forms), or they may remain connected, taking on various forms and functions, and so forming part of a tissue.

In recent years so much work on the cell has been done, so many theories have been suggested, so many new terms have been introduced, covering so many newly found structures and raising such special problems, that a reader of histological and cytological literature becomes very confused. It is as if the clue to all living problems were hidden in the cell, as if the microscope could disclose to us all the unknown springs of 'being'. This fashion is, however, already on the wane, and in a few decades the historical writer will find it difficult to wade through the extremely complicated terminology that has been introduced. His task will be a dull one, since the only interest that will then remain will be archaeological. Nevertheless, the influence of this cell-theory on other departments of biology must now be discussed.

The fact that every organism begins as a single cell, and that development is always accompanied by cell- division, added to the prestige of the cell theory. Every fact connected with cell-division was believed to have embryological significance. The method of segmentation of the egg was thought to be particularly important, and the different types of segmentation were used to subdivide the whole animal kingdom. These differences were later shown to be of secondary importance.

(a) Complete segmentation, when the whole egg divides into two cells, into four, and so on. Division may be equal, when the daughter cells are of the same size ; or unequal, when they differ in size. (b) Partial or incomplete segmentation. The egg here divides into two cells, of which the one, the greater, contains a great deal of yolk and little protoplasm ; the other, the less, chiefly protoplasm. The second smaller cell under- goes further division. Here the segmentation may be 'discoidal', when the division is confined to a small plate of cells at one end the so-called animal pole of the egg ; or 'superficial', when the surface of the egg undergoes

segmentation, the yolk remaining in the centre and taking no part in the division. Kolliker therefore divided animals into those in which the segmentation is complete (vertebrates, anthropods, gastropods, cephalopods), and those in which it is partial (worms, jellyfish, polyps, medusae). Van Beneden(i874) and Jager (1870) worked out similar classifications. The cell theory had considerable influence upon ideas about the nature of embryonic development. Since all the cells of the mature organism arise by repeated division and differentiation, it seemed as if it would be particularly useful to follow the development of each type of cell during the embryonic stages of growth. It was found that certain parts of the body, e.g. the epidermis, the sex cells, the innermost layer of the digestive tract, arise by con- tinued division from definite embryonic cells. Attempts were therefore made to follow the origin of all the elements of the body back as far as possible.

Sometimes these efforts were crowned with success. Boveri traced the origin of the sexual cells in the thread- worm of the horse to the four-celled stage of the blastula. One cell of the four-celled embryo gives rise, by repeated division, to the reproductive cells of the adult. In cyclops an arthropod the sex cells develop from one cell of the thirty-two-celled embryo. It was further found that when the segmentation is unequal, the smaller cells form the ectoderm, the larger the endoderm. In other cases the results obtained were not so simple. The muscular system, for example, which is so uniform in the adult animal, is sometimes formed from ectodermal cells, sometimes from endodermal, usually from the mesoderm. The true nerve cells arise from the ectoderm, the cells of the neurilemna, which are scattered among them, from the mesoderm. In these cases the developmental history seems of minor im- portance ; in the one case the same tissue is seen to arise from cells believed to be absolutely independent, while in the other case elements which form a uniform whole in the adult arise from two types of embryonic cell. These facts

tended to lessen the importance attached to the view that the history of individual cells is of absolutely fundamental significance in embryology; but it did not destroy it altogether. The task of following the history of the millions of cells, which become connected, divide, and move in a most com- plicated way, was seen to be a difficult one, but it was not abandoned, for it was believed that every cell in its normal development underwent a definite series of changes, and that these had been fixed by millions of years of heredity.

It was the study of the phenomena of regeneration that finally overthrew the belief in the importance of the cell theory for embryology. In some worms, for example, mesoderm cells were shown to be regenerated from ecto- derm cells ; and in general the fate of cells in regenerative processes is quite different from their fate in the normal course of development. In the early nineteenth century the vitalistic theory was still predominant ; a living principle was believed to dwell somewhere within each body, and to regulate all its activities. Bichat did not agree with this. He taught that for each tissue within the body there exists a separate vital principle. The cell theory brought with it the assumption that each cell of the body is a separate centre of activity. Virchow believed this implicitly, and adapted the idea to make it fit into his theory of the nervous system ; he held that there is no soul controlling the whole body, but that each nerve cell represents a separate centre of nervous control.

Towards the end of the century it seemed as if this idea was to receive strong confirmation. Earlier hypotheses as to the minute structure of the nervous system did not correspond well with Virchow's views. It was thought at that time Gerlach's name is particularly connected with these ideas that the whole nervous system consisted of nerve cells and their thread-like branches. These ramify in all directions, and then unite to form a network spread over the whole body, and particularly over the central nervous system. In the 'nineties, however, the Spanish histologist, Cajal, occupied himself with demonstrating that no such Gerlach network exists, but that the branches from each nerve cell remain quite separate. Their branches, he held, come into close contact with the branches from other cells, but never actually unite with them. This view was ultimately accepted by most histologists, including Kolliker. Waldeyer gave the name neuron to a nerve cell with all its branches, and hence the term neuron theory.

This assumed that there are as many separate centres of nervous activity as there are nerve cells. Each cell lives its own individual life. Branches, at their points of contact, pass on a stimulus from one nerve cell to another and so a stimulus is conducted. Nerve cells only differ from one another in size, in the number and direction of their branches, and in other similar material points of structure. Particular importance was attached to the fact that no differences in the nerve cells could be demonstrated which correspond to the obvious and striking differences between psychological processes.

The nervous system is only an aggregate of nerve cells. These have physiologically different functions ; one, some- how or the other, produces the sensation of redness, another of yellowness, others give the memory for words, &c. The most distinguished histologists accepted this theory. Physiologists like Helmholtz endeavoured to make their views harmonize with it. The psychologist Wundt raised no objection to it ; he found it capable of explaining certain of his difficulties.

Nevertheless the theory was incorrect ; the Hungarian histologist Apathy and the German psychologist Bethe were later able to show conclusively that Gerlach's idea of a network was more correct than is this idea of the neuron. Just as, formerly, the correctness of the neuron theory had been widely assumed, so now its incorrectness was demon- strated by many workers; to-day it interests us solely because it is so very characteristic of the thought of the nineteenth century. 1

Some Theories Relating to Structures which are Smaller than Cells. Every object of thought can be resolved into its 'elements' in two very different ways, according as these 'elements' differ from the whole object quantitatively or qualitatively. We can resolve the state into human beings, human beings into organs, the organs into tissues, tissues into cells, these into chemical compounds, into molecules, atoms, and so on ; or we can resolve human beings into body and soul, these into their separate sensations, and so on.

Analysis according to facts of time and space is purely quantitative. A body occupies a definite space and lives for a definite time. We can think of it as divided into elements which occupy a certain space, say I ccm. or I mm., and which live for a certain time an hour, a minute, or a second. However little we may know about the internal structure of the human body this we can assert a priori ; that there is no final unit of time or space into which that body can be subdivided. Philosophers have often dwelt on this theme.

The analysis of the human being into qualitatively different elements into soul and body, into organs and tissues bears no relation to quantitive analyses. Without our own subjective experience, the knowledge that each man thinks and feels much as we do, that he reveals a soul, we could not arrive at any such qualitative subdivision by considering the material facts of our existence. 1 A fuller account of the neuron theory will be found in Kolliker's Handbucb der Gewebelebre, edition 1 896. This also gives a full list of references to the litera- ture of the subject.

tissues had first to be discovered. He who has not seen the cells of the human body could not guess at their existence. Similarly, we might by chance guess that the air con- sists of small particles ; but no guess would suggest that it consists of oxygen and nitrogen. This fact had to be discovered. The men working out the cell theory were victims of the general human desire to substitute logical analysis for analysis of the actual facts of experience. Leibnitz, Buffon, Haller, Milne-Edwards, Oken had taught that the body is made up of minute invisible spheres, grains, fibrils and the like. Soon after the discovery that these ideas were false, and that it is composed of cells, workers fell into the same mistake again ; and they now looked for these ulti- mate spatial elements within the single cells. The materialistic tendencies of the times, together with the importance attached to microscopic work, encouraged the growth of this mode of thought.

Darwin indulged in this type of speculation. In order to make the mechanism of inheritance clear, he postulated that there are in the body minute invisible particles which are the carriers of hereditary qualities. These circulate freely in the body, collect in the reproductive cells, and so are passed on to the next generation. When the egg segments, these particles also divide, pass into the newly formed cells, and, arriving at definite positions in the developing organism, call forth there the properties which they have carried hidden within them.

To understand how Darwin came to postulate such a theory (which did not differ from those of the eighteenth century or for that matter from those of Aristotle), we must remember that he had no practical experience of the cell theory or of histological work. His contemporaries who had such knowledge received the theory unfavourably ; Huxley did not accept it, nor did Weismann, nor even Haeckel. It was not, however, his attempt to subdivide the body into minute spatial elements that roused their opposition, but rather the picture that he gave of the

circulation of these elements through the body when there was no known apparatus to render this possible. The belief that the cell contains definite properties, carried by definite material particles, was accepted, and formed an important part of the theory of evolution; Darwin called these particles gemmules (1868); Elsberg (1870) and Haeckel (1876) called them plastidules ; Herbert Spencer physiological units, De Vries (1889) pangenes. Francis Galton (1876) called them stirps. Weismann (1885) suggested that there is a whole series of them.

Other writers were less concerned with heredity ; their endeavour was simply to subdivide the organism into particles smaller than cells. Briicke (1861) was among these. He suggested that the cell consists of 'elementary particles'; Nageli( 1 884), Weisner ( 1 892), O. Hertwig( 1 906), and Altmann(i89o) discussed these under various names. Other workers thought it better to postulate certain physical structures and processes in the cell. Berthold (1877) likened protoplasm to a mixture of different liquids. Verworn (1901) attributed the properties of the living cell to the fluid nature of the protoplasm ; Hertwig and others rejected this view, and taught that the living portions of the protoplasm are solid aggregates. Haacke (1893) suggested that protoplasm consists of minute crystals. Biitschli's (1892) foam theory of the protoplasm was very widely accepted ; Flemming (1882) believed that it consists of fine threads. Many other similar hypotheses could be cited.

Every granule found in a cell was invested with the dignity of being the 'fundamental unit' of life. Special importance was attached to the chromatin and to the chromosomes formed from this. This arose from the fact that these elements are conspicuous in all dividing cells, that during cell-division they behave in a peculiar manner, and that at fertilization paternal and maternal chromo- somes unite. In addition, the desire was always in the minds of investigators to find some visible inheritable substance.

It came to be believed that the chromatin is the material substance connected with inheritance that it carries inherited characters from parents to offspring. The chro- mosomes were called 'character bearers'. Discussion then arose as to whether all the characters of an organism are contained in each chromosome of the egg, or whether each carries one group of characters (e.g. one the ectoderm, another the nervous system, another the teeth, and so on, Wilson, Boveri), or whether each contains all the characters of one organism the one carrying paternal characters, a second those of the grandfather, a third those of the great-grandfather, and so on (Rabl).

In recent years the fantastic idea that we come nearer and nearer to reality, the more we magnify the structures we are observing, has lost ground. Modern experimental morphology, the mutation theory, recent work on hybridi- zation, and other experimental lines of work have robbed microscopy of its peculiar importance. The cell theory became very important, especially in histology and embryology. The great aim of every re- search worker was to discover from which of the embryonic layers this or that tissue arose. Some there were, however, who felt the onesidedness of this method of attack. The wing of a bird, of a butterfly, of a bat all these have arisen from some cell ; but can we arrive at a real under- standing of them only by studying their cellular origin ? Is each tissue really to be regarded as an independent structure, following its own individual laws ?

Such were the questions which led some workers to oppose the cell theory. Sachs, the botanist, for example, tried to work out a new analysis of the cell, instead of accepting the view that it consists of various minute, invisible structures. Some cells may contain more than one nucleus liver cells generally have two; marrow cells and those of some pathological structures, some fungal cells, some cells found among the lower algae, the cells of certain Radiolaria and Infusoria, contain many, and may contain over 100 nuclei. This led Sachs to suggest that a simpler unit than the cell, consisting of a nucleus and its surrounding proto- plasm, is the 'living unit', out of which all organic life is formed. Kolliker (1897) agreed with this view, and the idea received a certain amount of favourable criticism. It was not widely accepted. Multi-nucleate cells were declared either to be exceptional structures, or, in certain cases, to represent an aggregate of several cells.

Heitzmann (1883) endeavoured to show that every living body be it an amoeba or be it a human body must be thought of as a uniform plasmatic whole, in which the living substance is spread out like a fishing-net, the knots representing cells. This attempt to substitute another view for that of the prevailing 'republic of cells' was not popular. A somewhat similar hypothesis was put forward by Pfliiger, the well-known physiologist. In botany the cell theory, however, soon lost its pre- eminence. In the work of Hofmeister, a contemporary of Darwin, we see a tendency to study the plant body as a unit, rather than to emphasize its separate parts. Sachs expressed this idea clearly when he discussed plant growth. He thought that growth, with the changes in form that accompany growth, is to be regarded as the primary phenomenon, and he tried to show how the laws of cell- division can be deduced from those of growth.

Cell-division sometimes takes place parallel to the surface of the growing organ (periclinal), sometimes at right angles to it (anticlinal), in such a way that in growing organs of spherical form the anticlinal walls are generally exactly radial, the periclinals forming a series of spherical surfaces parallel to the surface of the organ. Vegetative growing points have the form of a paraboloid of rotation, and in these anticlinal and periclinal walls form parts of confocal paraboloids. Thus the arrangement of the cells in any organ can be deduced from the shape of that organ.

S, Schwendener, although his point of view was rather different from that of Sachs, yet endeavoured to show that cell-division and cell arrangements are merely due to mechanical forces which are developed during the growth of the whole body. Other botanists, e.g. De Bary and Goebel, have held similar views. In the 'eighties, however, although such ideas were very prevalent among botanists, they found no favour with zoologists. In 1883 A. Rauber published a book on the cell, in which he gave the results of his own researches into the segmentation of the eggs of certain vertebrates ; in this he tried to introduce the botanical point of view into zoology. Rauber endeavoured to show that the whole organism must determine its parts, rather than the parts the individual cells the whole organism. Even among animals, he pointed out, the shape of the whole body enables us to deduce the form of its various elements (e.g. the shape of the whole bone enables us to infer the form of its separate Haversian systems). The animal body is not an aggregate; it is a unified protoplasmic whole, which during its development grows and divides in definite directions, separating into definite chemical and histo- logical units.