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Fig. 9

Diagram to illustrate spermatogenesis: a, showing the diploid number of chromosomes (six is arbitrarily chosen) as they occur in divisions of ordinary cells and spermatogonia; b, the pairing (synapsis) of corresponding mates in the primary spermatocyte preparatory to reduction; c, each secondary spermatocyte receives three, the haploid number of chromosomes; d, division of the secondary spermatocytes to form e, spermatids, which transform into f, spermatozoa.

Maturation of the Sperm-Cell.—In the maturation of the male gamete the germ-cell, now known as a spermatogonium, increases greatly in size to become a primary spermatocyte. In each primary spermatocyte the pairing of the chromosomes already alluded to occurs as indicated in Fig. 9b, p. 42, where six is taken arbitrarily to indicate the ordinary or diploid number of chromosomes, and three the reduced or haploid number. The division of the primary spermatocyte gives rise to two secondary spermatocytes (c), the paired chromosomes separating in such a way that a member of each pair goes to each secondary spermatocyte. Each secondary spermatocyte (d) soon divides again into two spermatids (e), but in this second division the chromosomes each split lengthwise as in an ordinary division so that there is no further reduction. In some forms the reduction division occurs in the secondary spermatocytes instead of the primary. Each spermatid transforms into a mature spermatozoon (f). The spermatozoa of most animals are of linear form, each with a head, a middle-piece and a long vibratile tail which is used for locomotion. The head consists for the most part of the transformed nucleus and is consequently the part which bears the chromosomes.

Maturation of the Egg-Cell.—As regards the behavior of the chromosomes the maturation of the ovum parallels that of the sperm-cell. There are not so many primordial germ-cells formed and only one out of four of the ultimate cells becomes a functional egg. As in maturation of the sperm-cell there is a growth period in which oögonia enlarge to become primary oöcytes (Fig. 10b, p. 45). In each primary oöcyte as in the primary spermatocyte the chromosomes pair and two rapidly succeeding divisions follow in one of which the typical numerical reduction in the chromosomes occurs. A peculiarity in the maturation of the ovum is that there is a very unequal division of the cytoplasm in cell division so that three of the resulting cells usually termed polar bodies are very small and appear like minute buds on the side of the fourth or egg-cell proper.

The scheme of this formation of the polar bodies is indicated in Fig. 10, p. 45. In Fig. 10b the chromosomes are seen paired and ready for the first division; that is, for the formation of the first polar body. Figs. 10c, d, p. 45, show the giving off of this body. Note that while only a small proportion of the cytoplasm passes into this tiny cell, its chromatin content is as great as that of the ovum. A second polar body (Figs. 10e, f, p. 45) is formed by the egg, but in this case each chromosome splits lengthwise, as in ordinary mitosis, and there is no further numerical reduction. In the meantime, typically, a third polar body is formed by division of the first. (Stages e, f, g.)

Parallel Between the Maturation of Sperm- and Egg-Cell.—This rather complex procedure of the germ-cells will be rendered more intelligible through a careful study of Figs. 9 and 10, pp. 42 and 45, and Fig. 11, p. 46, which indicates the parallel conditions in spermotogenesis and oögenesis.

Fig. 10

Diagram to illustrate oögenesis: a, showing the diploid number of chromosomes (six is arbitrarily chosen) as they occur in ordinary cells and oögonia; b, the pairing of corresponding mates preparatory to reduction; c, d, reduction division, giving off of first polar body; e, egg preparing to give off second polar body, first polar body ready for division; f, g, second polar body given off, division of first polar body completed. The egg nucleus, now known as the female pronucleus, and each body contain the reduced or haploid number of chromosomes.

The view now generally held regarding the polar bodies is that they are really abortive eggs. They later disappear, taking no part in embryo-formation. It can readily be seen how such an unequal division is advantageous to the large cell, for it receives all of the rich store of food material that would be distributed among the four cells if all were of equal size. This increased amount of food is a favorable provision for the forthcoming offspring whose nourishment is thus more thoroughly insured.

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Fig. 11

Diagram showing the parallel between maturation of the sperm-cell and maturation of the ovum.

On the other hand, all of the sperm-cells develop into complete active forms, which, as aforesaid, usually become very much elongated and develop a motile organ of some kind. In such cells an accumulation of food to any large extent would hinder rather than help them, because it would seriously interfere with their activity.

Fertilization.—In fertilization (Fig. 12, p. 48) the spermatozoon penetrates the wall of the ovum and after undergoing considerable alteration its nucleus fuses with the nucleus of the egg. In some forms only the head (nucleus) and middle-piece enter, the tail being cut off by a so-called fertilization membrane which forms at the surface of the egg and effectually blocks the entrance of other spermatozoa. Thus normally only one spermatozoon unites with an egg. In some forms while several may enter the egg only one becomes functional. As soon as the nucleus of the spermatozoon, now known as the male pronucleus, reaches the interior of the egg, it enlarges and becomes similar in appearance to the female pronucleus. It swings around in such a way (Fig. 12b, p. 48) that the middle piece, now transformed into a centrosome, lies between it and the female pronucleus. The two pronuclei (c, d, e), each containing the reduced number of chromosomes, approach, the centrosome divides, the nuclear walls disappear, the typical division spindle forms, and the chromosomes of paternal and maternal origin respectively come to lie side by side at the equator of the spindle ready for the first division or cleavage (f, g). It will be noted that the individual chromosomes do not intermingle their substance at this time, but that each apparently retains its own individuality. There is considerable evidence which indicates that throughout life the chromosomes contributed by the male parent remain distinct from those of the female parent. Inasmuch as each germ-cell, after maturation, contains only half the characteristic number of chromosomes, the original number is restored in fertilization.

Fig. 12

Diagram to illustrate fertilization; ♂, male pronucleus; ♀, female pronucleus; observe that the chromosomes of maternal and paternal origin respectively do not fuse.

Significance of the Behavior of the Chromosomes.—The question confronts us as to what is the significance of this elaborate system which keeps the chromosomes of constant size, shape and number; which partitions them so accurately in ordinary cell-divisions; and which provides for a reduction of their numbers by half in the germ-cell while yet securing that each mature gamete gets one of each kind of chromosome. Most biologists look on these facts as indicating that the chromosomes are specifically concerned in inheritance.

In the first place it is recognized that as regards the definable characters which separate individuals of the same species, offspring may inherit equally from either parent. And it is a very significant fact that while the ovum and spermatozoon are very unequal in size themselves, the chromosomes of the two germ-cells are of the same size and number. This parity in chromosomal contribution points clearly to the means by which an equal number of character-determiners might be conveyed from each parent. Moreover it is mainly the nucleus of the sperm-cell in some organisms which enters the egg, hence the determiners from the male line must exist wholly or largely somewhere in the nucleus. And the bulk of the nucleus in the spermatozoon consists of the chromosomes or their products.

A Single Set of Chromosomes Derived from One Parent Only Is Sufficient for the Production of a Complete Organism.—That a single or haploid set of chromosomes as seen in the gametes is sufficient contribution of chromatin for the production of a complete organism is proved by the fact that the unfertilized eggs of various animals (many echinoderms, worms, mollusks, and even the frog) may be artificially stimulated to development without uniting at all with a spermatozoon. The resulting individual is normal in every respect except that instead of the usual diploid number it has only the single or haploid number of chromosomes. Its inheritance of course is wholly of maternal origin. The converse experiment in echinoderms in which a nucleus of male origin (that is, a spermatozoon) has been introduced into an egg from which the original nucleus has been removed shows that the single set of chromosomes carried by the male gamete is also sufficient to cooperate with the egg-cytoplasm in developing a complete individual.

The Duality of the Body and the Singleness of the Germ.—Since every maternal chromosome in the ordinary cell has an equivalent mate derived from the male parent, it follows therefore, supposing the chromosomes do have the significance in inheritance attributed to them, that as regards the measurable inheritable differences between two individuals, the ordinary organism produced through the union of the two germ-cells is, potentially at least, dual in nature. On the other hand through the process of reduction the gametes are provided with only a single set of such representatives. This duality of the body and singleness of the mature germ is one of the most striking facts that come to light in embryology. How well the facts fit in with the behavior of certain hereditary characters will be seen later in our discussions of Mendelism.

The Cytoplasm Not Negligible in Inheritance.—Just what part is played by the cytoplasm in inheritance is not clear, but it is probably by no means a negligible one. The cytoplasm of a given organism is just as distinctive of the species or of the individual of which it forms a part as are the chromosomes. It is well established that neither nucleus nor cytoplasm can fully function or even exist long without the other, and neither can alone produce the other. They undoubtedly must cooperate in building up the new individual, and the cytoplasm of the new individual is predominantly of maternal origin. It is obvious that all of the more fundamental characters which make up an organism, such, for instance, as make it an animal of a certain order or family, as a human being or a dog or a horse, are common to both parents, and there is no way of measuring how much of this fundamental constitution comes from either parent, since only closely related forms will interbreed. In some forms, moreover, the broader fundamental features of embryogeny are already established before the entrance of the spermatozoon. It is probable therefore that instead of asserting that the entire quota of characters which go to make up a complete individual are inherited from each parent equally, we are justified only in maintaining that this equality is restricted to those measurable differences which veneer or top off, as it were, the individual. We may infer that in the development of the new being the chromosomes of the egg together with those derived from the male work jointly on or with the other germinal contents which are mostly cytoplasmic materials of maternal origin.

The Chromosomes Possibly Responsible for the Distinctiveness of Given Characters.—It seems probable that in the establishment of certain basic features of the organism the cooperation of the cytoplasm with chromatin of either maternal or paternal origin might accomplish the same end, but that certain distinctive touches are added or come cumulatively into expression through influences carried, predominantly at least, in the chromatin from one as against the other parent. These last distinctive characters of the plant or animal constitute the individual differences of such organisms. In this connection it is a significant fact that in young hybrids between two distinct species the early stages of development, especially as regards symmetry and regional specifications, are exclusively or predominantly maternal in character, but the male influence becomes more and more apparent as development progresses until the final degree of intermediacy is attained.

From the evidence at hand this much seems sure, that the paternal and maternal chromosomes respectively carry substances, be they ferments, nutritive materials or what not, that are instrumental in giving the final parity of personal characters which we observe to be equally heritable from either line of ancestry. It is clear that most of the characters of an adult organism can not be merely the outcome of any unitary substance of the germ. Each is the product of many cooperating factors and for the final outcome any one cooperant is probably just as important in its way as any other. The individual characters which we juggle to and fro in our breeding experiments seem apexed, as it were, on more fundamental features of organic chemical constitution, polarity, regional differentiation, and physiological balance, but since such individual characters parallel so closely the visible segregations and associations which go on among the chromosomes of the germ-cells it would seem that they, at least, are represented in the chromosomes by distinctive cooperants which give the final touch of specificity to those hereditary characters which can be shifted about as units of inheritance.

Sex and Heredity.—Whatever the origin of fertilization may have been in the world of life, or whatever its earliest significance, the important fact remains that to-day it is unquestionably of very great significance in relation to the phenomena of heredity. For in all higher animals, at least, offspring may possess some of the characteristics originally present in either of two lines of ancestry, and this commingling of such possessions is possible only through sexual reproduction. As has already been seen, in the pairing of chromosomes previous to reduction, the corresponding members of a pair always come together so that in the final segregation each gamete is sure to have one of each kind although whether a given chromosome of the haploid set is of maternal or paternal origin seems to be merely a matter of chance. Thus, for instance, if we arbitrarily represent the chromosomes of a given individual by ABC abc, and regard A, B and C as of paternal and a, b and c as of maternal origin, then in synapsis only A and a can pair together, B and b and C and c, but each pair operates independently of the other so that in the ensuing reduction division either member of a pair may get into a cell with either member of the other pairs. That is, the line up for division at a given reduction might be any one of the following, ^ABC⁄abc ^ABc⁄abC ^Abc⁄aBC ^AbC⁄aBc. This would yield the following eight kinds of gametes, ABC, abc, ABc, abC, Abc, aBC, AbC, aBc, each bearing one of each kind of chromosome required to cover the entire field of characters necessary to a complete organism. And since each sex would be equally likely to have these eight types of gametes and any one of the eight in one individual might meet any one of the eight of the other, the possible number of combinations in the production of a new individual from such germ-cells would be 8x8, or 64. With the larger numbers of chromosomes which exist in most animals it is readily seen that the number of possible combinations becomes very great. Thus any individual of a species with twenty chromosomes—and many animals, including man, have more—would have ten pairs at the reduction period and could therefore form (2)¹⁰, or 1,024 different gametes in each sex. And since any one of these in one sex would have an equal chance of meeting with any one in the opposite sex, the total number of possible different zygotes that might be produced would be (1,024)², or 1,048,576. Sex therefore, through recombinations of ancestral materials, undoubtedly means, among other things, the production of great diversity in offspring.

DETERMINATION OF SEX

Many Theories.—From earliest times the problem of sex determination has been one of keen interest, and needless to say hundreds of theories have been propounded to explain it. Geddes and Thomson say that Drelincourt recorded two hundred sixty-two so-called theories of sex production and remark that since his time the number has at least been doubled. The desirability of controlling sex has naturally appealed strongly to breeders of domesticated animals.

A study of animals born in litters, or of twins, is enough in itself to make us skeptical of theories of sex-determination based on nutritional or external factors. In a litter of puppies, for example, there are usually both males and females, although in their prenatal existence they have all been subject to the same nutritional and environmental conditions. Likewise in ordinary human twins one may be a boy, the other a girl, whereas if the nutritional condition of the mother were the fact determining sex, both should be boys or both girls. However, there are twins known as identical twins who are remarkably alike and who are always of the same sex. But there is reason to suppose that identical twins in reality come from the same zygote. Presumably in early embryogeny, probably at the two-celled stage of cleavage, the two blastomeres become separated and each gives rise to a complete individual instead of only the half of one it would have produced had the two blastomeres remained together. Such twins are monochorial; that is, they grow inside the same fetal membrane, whereas each ordinary twin has its own fetal membrane and has obviously originated from a separate ovum. It has been established experimentally in several kinds of animals that early cleavage blastomeres when isolated can each develop into a complete individual. In man, ordinary twins are no more alike than ordinary brothers and sisters, but identical twins are strikingly similar in structure, appearance, habits, tastes, and even susceptibility to various maladies. The fact that they are invariably of the same sex is a strong reason for believing that sex was already developed in the fertile ovum and consequently in the resulting blastomeres from that ovum.

The young of the nine-banded armadillo in a given litter are invariably of the same sex and are closely similar in all features. Newman and Patterson have shown that all the members of a litter come from the same egg. Patterson has established the fact that cleavage of the egg takes place in the usual manner, but later separate centers of development appear in the early embryonic mass and give rise to the separate young individuals.

Again in certain insects where one egg indirectly gives rise to a chain of embryos, or to a number of separate larvæ, possibly as many as a thousand, all of the latter are of the same sex. Even in some plants researches have shown that sex is already determined at the beginning of development. Then, too, much evidence has come to light recently showing that sex-characters in certain cases behave as heritable characters and are independent of external conditions. Lastly there is visible and convincing evidence obtainable through microscopical observations that sex is determined by a mechanism in the germ-cells themselves. It is chiefly to these latter facts that I wish to direct attention for the present.

The Sex Chromosome.—The evidence centers about a special chromosome or chromosome-group commonly designated as the sex-chromosome or X-element, which has been found in various species of animals, including man. In the males of such animals this chromosome is present in addition to the regular number of pairs, thus giving rise to an uneven instead of the conventional even number of chromosomes. This element remains undivided in one of the maturation divisions of the spermatocytes, in some forms in the first in others in the second, and passes entire to one pole of the spindle (Fig. 13, p. 58). This results in the production of two classes of cells, one containing the X-element and one not. The outcome is that two corresponding classes of spermatozoa are produced. The phenomena involved are diagrammatically represented in Fig. 13. It has been clearly demonstrated in several cases that eggs fertilized by spermatozoa which possess this X-element, always become females, those fertilized by spermatozoa which do not possess it always develop into males.

Fig. 13

Diagram illustrating the behavior of the x-element or sex-chromosome in the maturation of the sperm-cell. In one of the two maturation divisions (represented here as in the first) it passes undivided to one pole (a, b, c), in the other it divides. Since the cell without the x-element also divides the result is that ultimately from the original primary spermatocyte (a) four cells are formed (f), two with the x-element and two without it. Half of the spermatozoa therefore will bear an x-element, half will be without it. In a the ordinary chromosomes, arbitrarily indicated as 10, are supposed to have already paired for reduction so that the original diploid number in spermatogonia and body-cells of the male would be 20 plus the x-chromosome.

It has been found, furthermore, that in species in which the males possess this extra element the females have two of them. That is, if the original number in the somatic cells of the male were twenty-three, twenty-two ordinary and one X-element, the number in the somatic cells of the female would be twenty-four, or twenty-two ordinary and two X-elements. It has been found that when the chromosomes of the female pair for the reduction division, each chromosome uniting with its corresponding fellow, the two X-elements in the female pair in the usual way so that every egg-cell possesses an X-element. Thus every mature egg has an X-element, while only half of the spermatozoa have one. That is, if we assume twenty-three as the diploid number present originally in the somatic cells of the male and twenty-four as the number in the female, then one-half the spermatozoa of the male would contain the haploid number eleven, and the other half, the number twelve, whereas every mature ovum would contain twelve. Since there are equal numbers of the spermatozoa with the X-element and without it, and inasmuch as presumably under ordinary conditions one kind is as likely to fertilize the egg as the other, then there are equal chances at fertilization of producing a zygote with two X-elements or with but one.

Thus,	Spermatozoon + X by Ovum + X = Zygote + XX.
	Spermatozoon (no X) by Ovum + X = Zygote + X.

We have already seen that the former is always female, the latter male. It thus becomes possible to distinguish the sex of an embryo by counting the chromosomes of its cells. This has been accomplished in several cases.

In some instances[1] the conditions may be much more complex than the ones indicated—too complex in fact to warrant detailed discussion in an elementary exposition—but the principle remains the same throughout, the very complexity when thoroughly understood, strengthening rather than weakening the evidence. In a few forms an interesting reversal of conditions has been found in that the eggs instead of the spermatozoa show the characteristic dimorphism.

Just what the exact relationship between sex-differentiation and the X-element is has never been clearly established. It is possible that this element is an actual sex-determinant, in the ordinary cases one X-element determining the male condition and two X-elements producing the female condition. On the other hand it might be argued that it is not the determining factor but the expression of other cell activities which do determine sex; that is, a sex accompaniment. Or again, it may be one of several essential factors which must cooperate to determine sex.

SEX-LINKED CHARACTERS

The discovery of the remarkable behavior of certain characters in heredity which can only be plausibly explained by supposing that they are linked with a sex-determining factor still further strengthens our belief in the existence of such a definite factor. Such characters are commonly termed sex-linked characters.

Sex-Linked Characters in Man.—Since there are a number of them in man we may choose one of these, such as color-blindness, for illustration. The common form of color-blindness known as Daltonism in which the subject can not distinguish reds from greens, a condition which seems to be due to the absence of something which is present in individuals of normal color vision, is far commoner in men than in women. Its type of inheritance, sometimes termed “crisscross” heredity, has been likened to the knight moves in a game of chess. The condition is transmitted from a color-blind man through his daughter to half of her sons. Or, to go more into detail, a color-blind father and normal mother have only normal children whether sons or daughters. The sons continue to have normal children but the daughters, although of normal vision themselves, transmit color-blindness to one-half of their own sons. If such a woman marries a color-blind man, as might easily happen in a marriage between cousins, then as a rule one-half her daughters as well as one-half her sons will be color-blind.

Fig. 14

Diagram illustrating the inheritance of a sex-limited character such as color-blindness in man on the assumption that the factor in question is located in the sex-chromosome (from Loeb after Wilson). The normal sex-chromosome is indicated by a black X, the one lacking the factor for color perception, by a light X. It is assumed that a normal female is mated with a color-blind male.

In such cases what appears to be a mysterious procedure becomes very simple if we assume that the defective character is associated with the sex-determining factor, or to make it concrete let us say with the X-element. The chart shown in Fig. 14, p. 62, indicates what the germinal condition would be under the circumstances. The column to the right represents the maternal, the one to the left the paternal line. Since two X means female and one X male, and inasmuch as we have assumed that the physical basis of the defect to which color-blindness is due is conveyed by the X-element, we may represent the defective single X of the male in outline only (see first row). It is obvious that after the reduction divisions (second row) the mature sex-cells of the female will each contain a single normal X, the corresponding sex cells of the male will contain either no X or a defective X. Since if any member of the class of spermatozoa containing no X, fertilizes an egg the resulting zygote (row three) will have but one X and that a normal one, the individual which develops from the zygote will be normal as regards color vision and moreover will be male because the condition one X always means maleness. On the other hand, if any member of the class of spermatozoa containing the defective X fertilizes an egg two X-elements are brought together and this of itself means femaleness. In this case one of the X-elements is defective but the single normal X is sufficient in itself to produce normal color vision. But when it comes to the maturation of the sex-cells of this female, the pair of X-elements are separated in the usual way with the result that half of the mature ova contain a normal X and half a defective X (row four). Since in a normal male, however, the mature reproductive cells will contain either a normal X or no X (fourth row), any one of four different kinds of matings may result. A sex-cell carrying normal X of the male may combine with an ovum containing normal X producing a normal female (row five). Or such a cell may combine with an ovum carrying the defective X, also producing a female but one who although of normal color vision herself, like her mother, is a carrier of the defect. On the other hand, any one of the spermatozoa without an X may combine with an ovum containing the normal X, in which case a normal male is produced and, moreover, one who, like his mother’s brothers, is incapable of transmitting the defect. However, the sperm-cell devoid of an X is just as likely to fertilize an ovum carrying the defective X, in which event the resulting individual, a male, must be color-blind because he contains the defective X alone. In other words, the chances are that one-half the sons of a woman whose father was color-blind will be color-blind, the other half perfectly normal; and that all of the daughters will be of normal color vision although one-half of them will probably transmit the defect to one-half of their sons. From a glance at the diagram it is readily seen also that a color-blind female could result from the union of a color-blind man (see first row) and the daughter of a color-blind man (see third row). For half of the gametes of such a female would bear the defect as would also that half of the gametes of the male which carry X, hence the expectation would be that half of the daughters of such a union would be color-blind and half would be carriers of color-blindness; and that half of the sons would be color-blind and half normal. All the sons of a color-blind woman would be color-blind because she has only defective X-elements to pass on.

The inheritance of various other conditions in man follows more or less accurately the same course as color-blindness. Among these may be mentioned: hemophilia, a serious condition in which the blood will not clot properly, thus rendering the affected individual constantly liable to severe or fatal hemorrhage; near-sightedness (myopia) in some cases; a degenerative disease of the spinal cord known as multiple sclerosis; progressive atrophy of the optic nerve (neuritis optica); Gower’s muscular atrophy; some forms of night-blindness; in some cases ichthyosis, a peculiar scaly condition of the skin. In one of my own tabulations of a case of inheritance of “webbed” digits or syndactyly, a condition in which two or more fingers or toes are more or less united, a sex-linked inheritance is clearly indicated (Fig. 15), although from the pedigrees recorded by other investigators this condition usually appears in some of both the sons and daughters of an affected individual.

Fig. 15

Chart showing the inheritance of a case of syndactyly after the manner of a sex-linked character. The affected individuals are represented in black; squares indicate males, circles females. The condition is seen to be inherited by males through unaffected females.

The Occurrence of Sex-Linkage in Lower Forms Renders Experiments Possible.—The course followed by such characters in man can be inferred only from the pedigrees we can obtain from family histories. Fortunately, however, such sex-linkage also occurs in lower animals and we are able therefore to verify and extend our observations by direct experiments in breeding. Several sex-linked characters have been found to exist in a small fruit-fly known as Drosophila. Extensive breeding experiments with this fly by Professor T. H. Morgan and his pupils have borne out remarkably the interpretation that the characters in question are really linked with a sex-determining factor.