( Originally Published 1909 )
NO TOPIC in all biology has received so much attention in recent times, both from investigators and from the intelligent public at large, as Heredity. The reason for this interest is to be found in the importance of heredity for the individual human life, its practical importance in breeding plants and animals and its bearing on the evolutionary theory of biology. Its importance in these lines is clearly related by J. Arthur Thomson, of Aberdeen, in his recent book, 'Heredity': "There are no scientific problems of greater human interest than those of Heredity,' he declares, "that is to say, the genetic relation between. successive generations. Since the issues of the individual life are in great part determined by what the living creature is or has to start with, in virtue of its hereditary relation to Intents and ancestors, we cannot disregard the facts of heredity in our interpretation of the past, our conduct in the present or our forecasting of the future.. Great importance undoubtedly attaches to Environment in the widest sense food, climate, housing, scenery and the animate 'milieu'; and to Function in the widest sense, exercise, education, occupation or the lack of these; but all these potent influences act upon an organism whose fundamental nature is determined, tho not rigidly fixed, by its Heredity, that is, we repeat, by its genetic relation to its forebears. As Herbert Spencer said, 'Inherited constitution must ever be the chief factor in determining character.' And what is important in regard to Man's heredity is even more demonstrably important in regard to his domesticated animals and cultivated plants. What has been achieved in the past in regard to horses and cattle, pigeons and poultry, cereals and chrysanthemums, by experimental cleverness and infinite patience may be surpassed in the future if breeders and cultivators can attain to a better understanding of the more or less obscure laws of inheritance on which all their results depend.
"The study of heredity is also of fundamental importance in the domain of pure science, in the biologist's attempt to interpret the process of evolution by which the complexities of our present-day fauna and flora have gradually arisen from simpler antecedents. For heredity is obviously one of the conditions of evolution, of continuance as well as of progress. There would have been heredity even if there had been a monotonous world of Protists without any evolution at all, but there could not have been- any evolution in the animate world without heredity as one of its conditions. The study of heredity is inextricably bound up with the problems of development, reproduction, fertilization, variation and so on; in short, it is one of the central themes of Biology."
Some outline of the reproduction of organisms is a necessary prelude to a discussion of the theories of heredity. It has been stated that as a rule individual plants and animale start as a single cell. In the one-celled organisms the simple division of the parent cell into daughter cells constitutes reproduction. Each of the daughter cells thus formed is a young organism with the power to grow to mature size, divide and complete a life cycle by reproducing. One unicellular organism to-day may merge its individuality into two offspring in a ft w hours and then into four in the next few hours and so on.
Many-celled plants and animals begin their individual existence as one-celled ova or ovules which by oft-repeated cell-division produce the thousands of cells found in the body of the larger plants and animals. In these, certain cells are set apart as reproductive cells for the development of new individuals.
As is well known, most higher plants and animals have differentiated into male and female sexes. Each produces a peculiar kind of reproductive or germ cell. In animals the organs of the male known as spermaries produce minute cells (sperm-cells or spermatozoa), provided with a vibratile appendage capable of causing swimming in fluids. The organs of the female known as ovaries pro-duce ova or eggs. These eggs are simple cells, usually incapable of division without fertilization. By swimming a sperm cell comps into contact with an egg cell, penetrates and is transformed into a nucleus which moves to meet and fuse with the female nucleus of the egg-cell. This en-trance and fusion of sperm-nucleus with egg-nucleus is fertilization. Immediately after the fusion the fertilized egg or oosperm shows signs of preparation for division by mitosis and soon the two cell stage is formed. In like manner by mitosis cleavage again takes place in each of these two cells and there follow stages of four, eight, six-teen, thirty-two, etc., cells until the egg has been divided into a mass of cells. Cell-division continues, differentiation into tissues takes place and a folding off of organs goes on until the individual is completely formed.
In plants the process is in essentials the same. In the lower plants, even including the mosses and the ferns, the male germ-cells are motile and swim to meet the female germ-cells. They enter and produce changes similar to those described for animals. In the higher flowering plants motile male-cells are not found. Instead there, are pollen grains adapted to being carried by winds, insects, etc., from the anther of one flower to the pistil of another. From the pollen grain a delicate tube grows down into the ovary and into contact with the egg-cell or ovule of the plant. Down this tube moves a small cell from the inside of the pollen grain. Its nucleus fuses with the egg-nucleus, producing fertilization and leading soon to cell-division.
In brief outline, the above is the story of the usual origin of higher plants and animals in sexual reproduction. The essential point is that new individuals arise from two cells, one derived from each parent.
Exceptional cases do occur. Some multicellular animals like Hydra and certain worms may give rise to buds or divide into two or more new animals. This is similar to the power of many plants to reproduce from buds, shoots or cuttings. This process is known as asexual reproduction, in which also is classed the simple division of one-celled plants and animals. In most cases organisms with the power of asexual reproduction also multiply by sexual reproduction, but many plants seem to be able to multiply indefinitely by runners, tubers and so on.
Another exception to the general rule that higher individuals develop from the fusion of two germ cells is found Ong certain species of plant lice (Aphides), water fleas (small crustacea) and others which under certain conditions develop from unfertilized eggs. This is parthenogenesis. With the possible exception of certain scale in-sects, parthenogenesis among animals is always temporary and parthenogenetic generations are from time to time, usually in the fall, succeeded by a generation reproducing sexually. Among plants many species are believed to be permanently parthenogenetic.
When such cases are considered, it must be admitted that the vital processes may continue indefinitely simply by repeated division of the cells themselves, without the intervention of the act of fertilization; still, on the other hand, it is necessary to conclude, on account of the wide distribution throughout the whole organic kingdom of the phenomenon of fertilization, that this institution is of essential importance among the vital processes and that it is fundamentally connected with the life of the cell.
For an understanding of the problems of heredity the method of development, of sperms, 'spermatogenesis,' and of ova, 'oogenesis,' is necessary as well as the exact steps of the process by which an oosperm or unicellular embryo is formed by the union of the two sexual elements. In plants and animals both ovary and spermary are at first composed of cells of the ordinary kind, the primitive sex-cells, and it is only by the further development of these that the sex of the gonad is determined.
In he spermary the sex cells undergo repeated fission, forming what are known as the sperm mother cells, in which the number of chromosomes is constant in any given species. The sperm-mother-cell divides and the process of division is immediately repeated, the result being that each sperm mother cell gives rise to a group of four cells having half the normal number of chromosomes, the four cells so produced being the immature sperms. Thus the sperm or male gamete is a true cell, and is specially modifled in most cases for active movements. This mitotic division by which the number of chromosomes in the sperm-mother-cells is reduced by one-half is known as a reducing division.
As already stated, the ova also arise from primitive sex cells. These divide and give rise to the egg mother cells. The egg-mother-cells do not immediately undergo division, but remain passive and increase, often enormously, in size, by the absorption of nutriment from surrounding parts ; in this way each egg mother cell becomes an ovum. In addition to increase in the bulk of the protoplasm itself, a formation of plastic products usually goes on town immense extent and the ovum may attain a comparatively enormous size, as, for instance, in birds, in which the 'yolk' is simply an immense egg cell.
Such an ovum is incapable of being fertilized or of developing into an embryo; before it is ripe for conjugation with a sperm or able to undergo the first stages of segmentation it has to go through a process known as the maturation of the egg. Maturation consists essentially in a twice-repeated process of cell-division by mitosis, and by its means two small cells called polar cells are thrown off. The ovum has now lost a portion of its protoplasm, together with three-fourths of its chromatin, half having passed into the first polar cell and half of what remained into the second: the remaining one fourth of the chromatin takes on a rounded form and is distinguished as the female pronucleus. The formation of both polar cells takes place by a reducing division, so that while the immature ovum contains the number of chromosomes found in the ordinary cells of the species, the mature ovum, like the sperm, contains only one-half the normal number.
Shortly after, or in some eases before maturation, the ovum is fertilized by the conjugation with it of a single sperm. Sperms are produced in vastly greater numbers than ova, and it often happens that a single egg is seen quite surrounded with sperms, all apparently about to conjugate with it. It has, however, been found to be a general rule that only one of these actually conjugates.; the others, like the drones in a beehive, perish without falling the one function they are fitted to perform.
The sperm and egg nuclei approach one another and finally unite to form what is called the segmentation nucleus, the single nucleus of what is not now the ovum but the oosperm the impregnated egg or unicellular embryo. The fertilizing process is thus seen to consist of the union of two nuclear bodies, one contributed by the male gamete or sperm, the other by the female gamete or ovum. It follows from this that the essential nuclear matter or chromatin of the oosperm is derived in equal proportions from each of the two parents. Moreover, as both male and female pronuclei contain only half the number of chromosomes found in the ordinary cells of the species, the union of the pro-nuclei results in the restoration of the normal number to the oosperm.
Fertilization being thus effected, the process of segmentation, or division of the oosperm, takes place as described. The significance of these observed phenomena of maturation, fertilization and cell-division in modern theories of inheritance will be apparent.
The main facts of organic reproduction which are fundamental to a consideration of the modern problems of heredity having been outlined, a brief survey of some of the most prominent theories of heredity which have been advanced during the last two centuries will be given, after which attention will be directed to the present day problems of heredity, including 'Mendelism,' or the experimental study of heredity, and those cytological problems which have as their aim the identification of the inheritance material in the germ-cells.
It is not strange that of the many attempts at theories of heredity the early ones were essentially mystical and fell back on the supernatural to explain what could not be seen. Throughout the seventeenth and eighteenth centuries there prevailed a theory of preformation. The believers in this theory, men like Bonnet and Haller, maintained the preformations of the organism and all its parts within the egg. They regarded the apparent new formation of organs during development as an illusion, and held that development was merely an unfolding of this preformed miniature. Moreover, they believed that the germ contained not only a preformation of the organism into which it was to grow, but of successive generations as well. To quote from Thomson: "Preformed miniature lay within preformed miniature in ever-increasing minuteness, as if in a conjurer's box. Thus it was computed that Mother Eve must have included over 200,000 millions of homunculi, or sometimes it was Adam who was made to bear this burden. For according to one party, the ovists e.g., Malpighi it was the ovum that contained the miniature which had to be unfolded ; while according to others the animalculists it was the sperm which contained the preformed model." But how the germ came to have this preformed model they could not tell.
Caspar Friedrich Wolff was the first to raise a strong protest against the speculations of the preformationists and to advance a new theory. Appealing to facts, he showed that in the early stages of the chick's development: there was no visible hint of a preformed miniature, but that various organs made their appearance successively and gradually and were to be seen being formed. He held that there is a new formation, or 'epigenesis.' But how the germ that seems to start anew every time can develop as it does the upholders of the theory of epigenesis could not tell. For their ultimate explanations of heredity both schools fell back on the assumption of hyperphysical agencies as the earlier theorists had done before them.
Passing from these mystical interpretations of the phenomena of heredity, there are a whole series of theories which are in varying degrees scientific and may be fairly described by the general designation pangenesis. Thomson in 'The Science of Life' and in 'Heredity' gives good accounts of the various theories of heredity. From these works the material in this section has been taken. These theories all have this in common, that they seek to ex-plain the uniqueness of the germ-cell by regarding it as a center of contributions from different parts of the organism a collection of samples from the various organs. Spencer, Darwin, Jager, Galton, Brooks and others at one time or another contributed toward these theories.
In 1864 Spencer suggested the existence of 'physiological units' derived, from and capable of development into cells, and supposed that they accumulated in the germ-cells, which thus became in a conceivable sense miniature organisms. The best known theory of this class is the 'provisional hypothesis of pangenesis' enunciated by Dar-win in 1868. The main suggestions of this theory are as follows :
Every cell of the body, not too highly differentiated, throws off characteristic gemmules;
These multiply by fission, retaining their characteristics ;
They become specially concentrated in the reproductive elements in both sexes;
In development the gemmules unite with others like themselves, and grow into cells like those from which they were originally given off, or they remain latent during development through several generations.
By means of this theory Darwin attempted to explain not only the simpler facts of heredity, but also "those very curious but abundant cases in which a character is transmitted in a latent form and at last reappears after many generations, such cases being known as 'atavism,' or 'reversion'; and again, those cases of latent transmission in which characteristics special to the male are transmitted to the male offspring through the female parent without being manifest in her; and yet again, the appearance at a particular period of life of characters inherited and remaining latent in the young organism," as Lankester expresses it.
The great defect of this theory is obviously its entirely hypothetical character no one has ever observed any gemmules. Moreover, it is not in harmony with the results of experiments e.g., on transfusion of blood or with what is known of the physiology of cells or with the facts of experimental inheritance.
The next theory to be noted is the theory of Genetic or Germinal Continuity. This theory was first suggested by Owen in 1849. Since then Hackel, Jager, Brooks, Galton, Nussbaum, Weismann, and a score of others have contributed toward it.
In its earlier conception this germinal continuity consisted in a continuity of germ-cells. A summary of this idea follows.
At an early stage in the embryo, the future reproductive cells of the organism are often distinguishable from those which. are forming the body.
The latter develop in manifold variety and lose almost all likeness to the mother germ.
The former the reproductive rudiments are not implicated in the differentiation of the 'body,' remain virtually unchanged, and continue the protoplasmic tradition unaltered.
As the sex-cells of the offspring are thus continuous with the parental sex-cells which give rise to it, they will in turn develop into similar organisms.
In this view the reproductive cells form a continuous chain and the reproduction of like by like is natural and necessary. But a serious difficulty besets this doctrine, for a direct chain of cellular continuity can only be said to exist in a few cases. Thus this theory of the continuity of the germ-cells has been replaced by the newer theory of the continuity of the germ-plasm.
This is Weismann's theory. Weismann has worked it out in the minutest details. The problems which he discusses are too intricate and technical for any but a special student. For present purposes a very brief summary as expressed by Thomson will be sufficient.
"A living creature usually takes its origin from a fertilized egg-cell, from a union of an ovum and a spermatozoon. These germ cells are descended by a continuous cell division from the fertllized ova which gave rise to the two parents; they have retained the organization of the fertilized ova, and this organization has its vehicle in the chromatin of the nucleus the germ plasm. This germ plasm consists of several chromosomes or idants, each of which is made up of several pieces or ids, each of which (here hypothesis begins) is supposed to contain all the potentialities generic, specific, and individual of a new organism. Each id is a microcosm with an architecture which has been elaborated for ages; it is supposed to consist of numerous determinants, one for each part of the organism that is capable of varying independently or of being independently expressed during development.
Lastly, each determinant is pictured as consisting of a number of ultimate vital particles of biophores, which are eventually liberated in the cytoplasm of the various embryonic cells. All these units of various grades are capable of growth and of multiplication by division."
In its more general aspects this view of Weismann's represents what might be called the dominant modern view. That is, there is general belief that the germ-cell inherits from the parental germ-cells an organization of great complexity, including an intricate architecture of minute particles which are the material bearers of particular inheritance qualities. Not all biologists, however, agree with Weismann in his limitation of the inheritance material to the chromosomes, It is here that the inheritance problems of to-day have their beginning.
Much attention has in recent years been given to the experimental study of variation and heredity. These experiments are of interest in connection with Mendel's law, a law so important in the science of biology that Professor Bateson has written of it, "The experiments which led to this advance in knowledge are worthy to rank with those that laid the foundation of the atomic laws of chemistry." The discoverer of this law was Gregor Johann Mendel (1822-1884), an Augustinian monk. He was a . man of varied interests, and in his gardens performed many hybridization experiments on plants. In 1866 he published a paper giving the results of his experiments, entitled 'Experiments in Plant Hybridization.' This paper did not attract much attention at the time, probably be-cause of the enthusiasm and the controversy evoked by the natural selection theory, and lay practically unknown in the Proceedings of the Natural History Society of Brünn for over thirty years. A revival of interest in the experimental study of variation and heredity at about the beginning of the present century led to the rediscovery of the Mendelian principles of heredity by several botanists working separately, and about that time Bateson brought into prominence Mendel's work and by a long series of experiments confirmed and extended it.
To gain an idea of the scope of these principles one cannot do better than turn to Mendel's own account of his experiments. Punnett's 'Mendelism' and Thomson's 'Heredity' give such an account, and from these sources the following statements have largely been taken.
In the selection of a plant for experiment Mendel recognised that two conditions must be fulfilled. In the first place, the plant must possess differentiating characters, and secondly, the hybrids must be protected from the influence of foreign pollen during the flowering period. In the edible pea Mendel found an almost ideal plant to work with. The separate flowers are self-fertilizing, while complications from insect interference are practically non-existent. As is well known, there are numerous varieties of the eating-pea exhibiting characters to which they breed true. In some varieties the seed color is yellow, while in others it is green. In some varieties the seeds are round and smooth when ripe; in others they are wrinkled. Some peas have purple, others have pure white flowers. Some peas again, when grown under ordinary conditions, attain to a height of 6 to 7 feet, while others are dwarfs which do not exceed 1 1/2 to 2 feet.
Mendel selected a certain number of such differentiating characters and investigated their inheritance separately for each character. Thus in one series of experiments he concentrated his attention on the heights of the plants. Crosses were made between tall and dwarf varieties, which previous experience had shown to come true to type with regard to these characters. It mattered not which was the pollen-producing and which the seed-bearing plant. In every case the result was the same. Tall plants resulted from the cross. For this reason Mendel applied the terms 'Dominant' (D) and `Recessive' (R) to the tall and dwarf habits respectively.
In the next generation the cross-bred plants (products of D and R or R and D, but all apparently like D) were allowed to fertilize themselves, with the result that their offspring exhibited the two original forms, on the average three dominants to one recessive. Out of 1,064 plants, 787 were tall, 277 were dwarfs.
When these recessive dwarfs were allowed to fertilize themselves they gave rise to recessive dwarfs only for any number of generations. The recessive character bred true.
When the dominants, on the other hand, were allowed to fertilize themselves, they produced one third of 'pure' dominants (producing dominants only when self fertilized) and two-thirds of crossbred dominants, which on self-fertilization again gave rise to a mixture of dominants and recessives in the proportion of 3: 1.
If in an experiment with mice a gray house-mouse is crossed with a white mouse, the offspring are all gray. Grayness is dominant ; albinism is recessive. The gray hybrids are inbred; their offspring are gray and white in the proportion 3:1. If these whites are inbred they show themselves 'pure,' for they produce whites only for subsequent generations. But when the grays are inbred they show themselves of two kinds, for one-third of them produce only grays, which go on producing grays; while the other two-thirds, apparently the same, produce both grays and whites. And so it goes on.
In his exceedingly clear exposition of Mendelism (1905) R. C. Punnett states the result thus: "Wherever there occurs a pair of differentiating characters, of which one is dominant to the other, three possibilities exist: there are recessives which always breed true to the recessive character; there are dominants which breed true to the dominant character, and are therefore pure; and thirdly, there are dominants which may be called impure, and which on self-fertilization (or inbreeding, where the sexes are separate) give both dominant and recessive forms in the fixed proportion of three of the former to one of the latter."
To explain such phenomena Mendel suggested that the hybrid produces in equal numbers two kinds of germ-cells (two kinds of egg cells or two kinds of pollen grains) that there is is in the developing reproductive organ a segregation of germ-cells into two equal camps, one camp with the potential quality of tallness, the other camp with the potential quality of dwarfness. Thus, if there are six ovules, three contain in their egg-cell the primary constituent corresponding to tallness, and three contain the primary constituent corresponding to dwarfness. Each of these is pollinated by a pollen grain, which, by hypothesis, contains the potential quality of tallness or of dwarfness; and if the two kinds of pollen-grains are present in equal numbers, each ovule has an equal chance of being fertilized by a pollen-grain with a potential quality of tallness or by a pollen-grain with a potential quality of dwarfness. Therefore the result must be a set of of-spring partly dominant and partly recessive in the pro-portions of 3:1.
Mendel discovered an important set of facts, and he also suggested a theoretical interpretation the theory of gametic segregation. As Bateson says, "The essential part of the discovery is the evidence that the germ-cells or gametes produced by cross-bred organisms may in respect of given characters be of the pure parental types, and consequently incapable of transmitting the opposite character; that when such pure similar gametes of opposite sexes are united in fertilization, the individuals so formed and their posterity are free from all taint of the cross; that there may be, in short, perfect or almost perfect discontinuity between these germs in respect of one of each pair of opposite characters."
This law of the segregation of gametes accords well with the experimental and observed phenomena of heredity. But this brings up the question, Is there any known process by which such a segregation could be brought about during the history of the germ-cells? "Is it," says Thomson, "enough simply to say that the germ-cells are little living unities with an organization, an equilibrium of their own, and that they tend as they multiply to become more stable namely, by separating out incompatibilities (dominant and recessive potential unit characters) and becoming the vehicle of either the one or the other? Are there differential divisions during the development of the germ-cells which lead to there being two camps of gametes which we may briefly describe as pure potential dominants and pure potential recessives? Is this not a possible expression of a struggle between the hereditary items and in line with Weismann's theory of germinal selection?"
"A more precise suggestion," says T. H. Morgan, "to which it seems too soon to attach great significance, is the fascinating hypothesis that the segregation occurs during the maturation division. If we assume that the chromosomes are the vehicles of the hereditary qualities, which seems highly probable ; if we assume, further, that a particular potential unit character is contained in each germ-cell in one chromosome and not in others, which seems a difficult assumption ; then it is possible that Sutton may be correct in his suggestion that the segregation of gametes into two sets occurs in the course of the maturation division."
A great deal of work confirming Mendel's experiences has been done both with plants and animals in laboratories in many countries, with the result that altho there are some difficulties and not a few discrepancies, "the truth of the law," as Bateson says, "is now established for a large number of cases of most dissimilar character."
On the other hand, there has been much experimentation in which the results do not harmonize with the Mendelian results. Thomson says : "There seems at present no reason to believe that the Mendelian formula has more than a limited application, tho it is of course possible that apparent exceptions may eventually turn out to be less formidable than they seem. There seems no reason why there should not be several formulae of inheritance, each applicable to particular sets of cases e.g., to cases where blending does occur and to cases where it never occurs. As the method of experiment is obviously the surest line of progress, the more it is prosecuted the sooner will the mists surrounding heredity disappear, but progress cannot be secured by ignoring difficult cases or by straining the formula in the eager desire to universalize it."
Extensive theoretical and practical applications of Mendel's law to problems of biology have been made. For the technical discussion of Mendel's law in connection with persistence in evolution and in relation to definite variations, reference must be made to some of the detailed studies on Mendelism. The following illustrations from Thomson and from Punnett will show its value to practical breeders.
Some kinds of wheat are very susceptible to the fungoid disease known as 'rust'; others are immune. The quality of immunity to rust is recessive to the quality of predisposition to rust. When an immune and a non-immune strain are crossed together the resulting hybrids are all susceptible to 'rust.' On self fertilization such hybrids produce seed from which appear dominant 'rusts' and recessive immune plants in the expected ratio of 3: I. From this simple experiment the phrase 'resistance to disease' has acquired a more precise significance, and the wide field of research here opened up in this connection promises results of the utmost practical as well as theoretical importance.
"The new science of heredity has much to teach the practical man," says Punnett. "Let us suppose that he has two varieties, each possessing a desirable character, and that he wishes to combine these characters in a third form. He must not be disappointed if he makes his cross and finds that none of the hybrids approach the ideal which he has set before himself ; for if he raises a further generation he will obtain the thing which he desires. He may, for example, possess tall green-seeded and dwarf yellow-seeded peas, and may wish to raise a strain of green dwarfs. He makes his cross and nothing but tall yellows result. At first sight he would appear to be further than ever from his end, for the hybrids differ more from the plant at which he is aiming than did either of the original parents.
"Nevertheless, if he sow the seeds of these hybrids he may look forward with confidence to the appearance of the dwarf green. And owing to the recessive nature of both greenness and dwarfness, he can be certain that for further generations the dwarf greens thus produced will come true to type. The green dwarfs are all fixed as soon as they appear, and will throw neither talls nor yellows. The less the hybrid resembles the form at which the breeder aims, the more likely is that form to breed true when it appears in the next generation.
In the years since 1900 there has been deep interest in the microscopic study of germ-cells in the search for the mechanism of heredity. Much observation and experimentation has been done and there has been a rapid advance in knowledge, but so intricate are the questions involved that investigation is most difficult and only a start at the problems has been made. In an address before the American Association for the Advancement of Science in December, 1907, E. G. Conklin well summarizes the arguments in support of the two general views der which opinions concerning the material bearers of inheritance may be said to be grouped, namely, the view that the chromosomes of the germ-cell are the bearers of heredity and the view that inheritance may take place through the cytoplasm of the germ-cells. A few of the less 'cal paragraphs of this paper are as follows:
"In practically all theories of heredity it is assumed that there is a specific 'inheritance material,' distinct from the general protoplasm, whose function is the 'transmission' of hereditary properties from generation to generation, and whose characteristics, as compared with the general protoplasm, are greater stability, independence and continuity. This is the Idioplasm of Nageli, the Germ plasm of Weismann. It is further assumed that this germ plasm is itself composed of ultramicroscopical units, which are capable of undergoing transformation during the course of development into the structures of the adult. However necessary such units may be for a complete philosophical explanation of development, it must be confessed that at present they constitute a purely hypothetical system which may or may not correspond to reality. We know that the germ cells are exceedingly complex, that they contain many visible units such as chromosomes, chromomeres and microsomes, and that with every great improvement in the microscope and in microscopical technique other structures are made visible which were in-visible before, and whether the hypothetical units just named are present or not seems to be a matter of no great importance, seeing that, so far as the analysis of the microscope is able to go, there are differentiated units which are combined into a system in short, there is organization.
"On the other hand, the evidence in favor of an inheritance material, which is distinct from the general protoplasm of the germ and whose function is the reproduction of hereditary characters, is not convincing. All the living substance of the egg cell is converted into the mature organism. That there is a species plasm or an individual plasm which is continuous from generation to generation, and from which all the qualities of the mature organism are differentiated, is almost a certainty, but there is no satisfactory evidence that this substance is distinct from the general protoplasm of the young germ-cells.
"Differentiation, and hence heredity, consists in the main in the appearance of unlike substances in protoplasm and their localization in definite regions or cells.
"Unfortunately, we do not know many of the steps by which different substances appear within protoplasm. But in all cases which have been carefully studied one significant fact appears, viz., the importance of the inter-action of the nucleus and cytoplasm. In many cases various substances have been seen to come out of the nucleus and to mingle with the cytoplasm, while the nucleus in turn absorbs substances from the cytoplasm. It is known that constructive metabolism, differentiation and regeneration never occur in the absence of a nucleus.
"Turning now to the differentiations of the fertilized egg cell, we find that different substances appear in the egg cell and become localized in different regions of the egg or embryo. It is known that there is an active inter-change of nuclear and cytoplasmic substances. In the long growth period of the egg the nucleus grows enormously, evidently at the expense of substances received from the cell body. On the other hand, it is well established that substances issue from the nucleus into the cell body and mingle with the cytoplasm during this stage.
"Finally, we may conclude that the nucleus plays a less important role in the localization of different substances than in the formation of those substances. Nevertheless, in differentiation, as well as in metabolism, there is every reason to believe that the entire cell is a physiological unit. Neither the nucleus nor the cytoplasm can exist long in-dependently of the other; differentiations are dependent upon the interaction of these two parts of the cell; the entire germ-cell, and not merely the nucleus or cytoplasm, is transformed into the embryo or larva; and it therefore seems necessary to conclude that both nucleus and cytoplasm are involved in the mechanism of heredity.
"It may be considered as definitely settled that the early development of animals is of purely maternal type, and that it is only after the broad outlines of development and the general type of differentiation have been established that the influence of the spermatozoon begins to make itself felt; and it is equally certain that this type of differentiation is predetermined in the cytoplasm of the mature egg cell rather than in the egg nucleus.
"On the other hand, there is no doubt that the differentiations of the egg cytoplasm have arisen, in the main, during the ovarian history of the egg, and as a result of the interaction of nucleus and cytoplasm; but the fact remains that at the time of fertilization the hereditary potencies of the two germ-cells are not equal, all the early development, including the polarity, symmetry, type of cleavage, and the relative positions and proportions of future organs, being predetermined in the cytoplasm of the egg-cell, while only the differentiations of later development are influenced by the sperm. In short, the egg cytoplasm fixes the type of development and the sperm and egg nuclei supply only the details.
"This conclusion is not a refutation of the nuclear inheritance theory, but it is a profound modification of it. At once it destroys the argument that since there is equality of inheritance from both parents there must be equivalence of inheritance material in egg and sperm. So far as those characteristics are concerned which appear late in development, it is highly probable that there is equality of inheritance from both parents, but in the early and main features of development, hereditary traits, as well as material substance, are derived chiefly from the mother.
"In the light of the conclusion that only the later and more detailed differentiations are influenced by the sperm, it follows that experimental work which aims to modify the fundamental features of an organism must be directed to the ovarian egg rather than to the sperm or to the developing embryo."
In conclusion, the following paragraphs from E. B. Wilson's 'The Cell in Development and Inheritance' will indicate the present state of the cytological study of inheritance problems and the outlook for the future. "We have now arrived," he says, "at the farthest outposts of cell-research, and here we find ourselves confronted with the same unsolved problems before which the investigators of evolution have made a halt. For we must now inquire what is the guiding principle of embryological development that correlates its complex phenomena and directs them to a definite end. However we conceive the special mechanism of development, we cannot escape the conclusioa that the power behind it is involved in the structure of the germ plasm inherited from foregoing generations.
"What is the nature of this structure and how has it been acquired? To the first of these questions we have as yet no certain answer. The second question is merely the general problem of evolution stated from the stand-point of the cell theory. The first question raises once more the old puzzle of preformation or epigenesis. The pangen hypothesis of de Vries and Weismann recognises the fact that development is epigenetic in its external features; but, like Darwin's hypothesis of pangenesis, it is at bottom a theory of preformation, and Weismann expresses the conviction that it is an impossibility.
"The truth is that an explanation of development is at present beyond our reach. The controversy between preformation and epigenesis has now arrived at a stage where it has little meaning apart from the general problems of physical causality. What we know is that a specific kind of living substance, derived from the parent, tends to run through a specific cycle of changes during which it transforms itself into a body like that of which it formed a part; and we are able to study with greater or less precision the mechanism by which that transformation is effected and the conditions under which it takes place. But despite all our theories, we no more know how the organization of the germ-cell involves the properties of the adult body than we know how the properties of hydrogen and oxygen involve those of water. So long as the chemist and physicist are unable to solve so simple a problem of physical causality as this, the embryologist may well be content to reserve his judgment on a problem a hundredfold more complex.
"The second question, regarding the historical origin of the idioplasm, brings us to the side of the evolutionists. The idioplasm of every species has been derived, as we must believe, by the modification of a preexisting idioplasm through variation and the survival of the fittest. Whether these variations first arise in the idioplasm of the germ cells, as Weismann maintains, or whether they may arise in the body cells and then be reflected back upon the idioplasm, is a question to which the study of the cell has thus far given no certain answer. Whatever position we take on this question, the same difficulty is encountered, namely, the origin of that coordinated fitness, that power of active adjustment between internal and external relations, which, as so many eminent biological thinkers have insisted, overshadows every manifestation of life. The nature and origin of this power is the fundamental problem of biology.
"It may be true, as Schwann himself urged, that the adaptive power of living beings differs in degree only, not in kind, from that of unorganized bodies. It is true that we may trace in organic nature long and finely graduated series leading upward from the lower to the higher forms, and we must believe that the wonderful adaptive manifestations of the more complex forms have been derived from simpler conditions through the progressive operation of natural causes. But when all these admissions are made, and when the conserving action of natural selection is in the fullest degree recognised, we cannot close our eyes to two facts : first, that we are utterly ignorant of the manner in which the idioplasm of the germ cell can so respond to the influence of the environment as to call forth an adaptive variation; and second, that the study of the cell has on the whole seemed to widen rather than to narrow the enormous gap that separates even the lowest forms of life from the inorganic world.
"I am well aware that to many such a conclusion may appear reactionary or even to involve a renunciation of what has been regarded as the ultimate aim of biology. In reply to such a criticism, I can only express my conviction that the magnitude of the problem of development, whether ontogenetic or phylogenetic, has been under estimated ; and that the progress of science is retarded rather than advanced by a premature attack upon its ultimate problems. Yet the splendid achievements of cell research in the past twenty years stand as the promise of its possibilities for the future, and we need set no limit to its advance. To Schleiden and Schwann the present standpoint of the cell-theory might well have seemed unattainable. We cannot foretell its future triumphs, nor can we doubt that the way has already been opened to better understanding of inheritance and development."