The Organism as a Whole, from a Physicochemical Viewpoint

Steinach in another series of experiments castrated young male rats and transplanted into them the ovaries of young females. These ovaries did not disintegrate, the eggs remaining, and corpora lutea were formed. In such feminized individuals the seminal vesicles, prostate, and penis did not reach their normal development, and it was thereby proved that the internal secretions from the ovary do not promote the growth of the secondary sexual male characters. On the contrary, Steinach was able to show that the growth of the penis was directly inhibited by the ovary, since in the feminized males this organ remained smaller than in the merely castrated animals. On the other hand the infantile uterus and tube when transplanted into the young male with the ovaries grow in a normal way, and Steinach thinks that pregnancy in such feminized males is possible if sperm be injected into the uterus. In some regards the feminized males showed the morphological habitus of females. Soon after the transplantation of ovaries into a castrated male the nipples of its mammary glands begin to grow to the large size which they have in the female and by which the two sexes can easily be discriminated. In addition the stronger longitudinal growth of the body in the male does not occur in the feminized specimens, the body growth becomes that of a female; and likewise the fat and hair of the feminized male resemble that of a real female.

While the castrated males show an interest in the females, the feminized males are absolutely indifferent to females and behave like them when put together with normal males ; and, what is more interesting, they are treated by normal males like normal females. The sexual instincts have, therefore, also been reversed in the feminized males by the substitution of ovaries for testes. The inhibition of the growth of the penis by the ovary is of importance ; it supports the idea already expressed that in hermaphrodites this inhibition of the growth of the secondary organs of the other sex is only feeble or does not exist at all.

We may finally ask whether there is any connection between the cytological basis of sex determination by special sex chromosomes and the physiological basis of sex determination by specific substances or internal secretions. It is possible that the sex chromosomes determine or favour, in a way as yet unknown, the formation of the specific internal secretion discussed in the second part of this chapter. In this way all the facts of sex determination might be harmonized, and it may become clear that when it is possible to modify secretions by outside conditions or to feed the body with certain as yet unknown specific substances the influence of the sex chromosomes upon the determination of sex may be overcome.

i. The scientific era of the investigation of heredity begins with Mendel's paper on plant hybridization which was not appreciated by his contemporaries. Mendel invented a method for the quantitative study of heredity which consisted essentially in crossing two forms of peas differing only in one well-defined hereditary character; and in following statistically and separately the results of this crossing and that of the inbreeding of the second and third generations of hybrids. This led him to the recognition of one essential feature of heredity; namely, that while the hybrids of the first generation are all alike, each hybrid produces two types of sex cells in equal numbers, one for each of the pure breeds which has been used for the crossing. This takes place not only when the forms used for the crossing differ in regard to one

1 For the literature on the subject the reader is referred to Morgan, T. H., Sturtevant, A. H., Muller, H. J., and Bridges, C. B., The Mechanism of Menddian Heredity. New York, 1915. character only but also if they differ for two or more characters. The statement made is Mendel's law of heredity, or, more correctly, Mendel's law of the segregation of the hereditary characters of the parents in the sex cells of the hybrids.1 Mendel's law allows us to tabulate and calculate beforehand the relative number of different forms which appear if the offspring of a mating of two varieties are bred among themselves. In order to do this it must be remembered also that while in some cases the hybrid is an intermediate between the two parent forms, in other cases it cannot be discriminated from one of the two parent forms. In such cases the character which appears in the hybrid was called by Mendel the dominant character and the one which disappeared the recessive character. According to Bateson, who was the first to systematize the phenomena of Mendelian heredity, recessiveness means generally the absence of a character which is present in the dominant type. When, e. g., the cross between a tall and a dwarf form of pea gives in the first generation only tall peas, on the basis of the presence and absence theory the dominant form contains a factor for growth which is lacking in the dwarf form. While this theory fits many cases it meets with difficulties in others. Thus the presence of a factor

1 Mendel, G., "Experiment in Plant-Hybridization," translated in W. Bateson's classical book on Mendel's Principles of Heredity. Cambridge, 1909. for pigment should be dominant over the absence of such a factor, which is usually the case, inasmuch as the cross of a coloured rat or rabbit with an albino is black or coloured. There is, however, also a case where whiteness is dominant over colour, as we shall see later. This fact does not necessarily contradict the presence and absence theory.1

When two pure breeds of parents differ in one character, e. g.j two varieties of beans, one with a violet the other with a white flower, the cross between the two species (the Fx generation) has pale violet flowers, approximately intermediate between the two parents. If these hybrids are bred among themselves the offspring is called the F2 generation. According to Mendel's law the hybrids of the first Fx generation all have two kinds of eggs in equal numbers, one kind representing the pure breed of the parents with violet, the other of the pure breed with white flowers. The same is true for the pollen cells. Hence the following possible combinations must appear in the offspring when the pale violet hybrids are inbred: violet white . .

1 The reader will find a critical discussion of the presence and absence theory on page 220 of Morgan, Sturtevant, Muller, and Bridges, The Mechanism of Mendelian Heredity. New York, 1915. (2) violet — white; (3) violet — white; (4) white — white. The first will result in pure violet flowers, the fourth in pure white, and the second and third in pale violet flowers. Since all four combinations will appear in equal numbers when the number of crossings is sufficiently large the numerical result will be:

Fifty per cent, of the F3 generation will be pale violet, 25 per cent, violet, and 25 per cent, white. The violets and whites each will breed true when bred among themselves since they are pure, and produce only one type of eggs and pollen. The pale violets are hybrids and will again produce the two types of eggs and pollen, that is, if bred among themselves will again give violets, pale violets, and whites in the ratio 1 : 2 : 1 . This the experiment confirms.

As has been stated, it not infrequently happens that all the hybrids of the first generation are alike. In such cases the one character is "recessive, " i.e., overshadowed or covered by the other the "dominant" character, which alone appears in the hybrids. Thus when Mendel crossed peas having round seeds with peas having angular seeds all the hybrids had round seeds. The round form is dominant, the angular recessive, i. £., all the hybrids have round seeds. When these hybrids were bred among themselves the next genera-

tion produced round and angular seeds in the ratio of 3:1 (5474 round to 1850 angular). The explanation is as follows. Let R denote round, A angular character ; the pure breeds of parents have the gametic constitution RR and AA respectively. When crossed, all the offsprings have the constitution RA and since A is recessive this hybrid generation resembles the pure RR parents. The Fx generation produces two kinds of eggs R and A and two kinds of pollen R and A in equal numbers, and these if inbred give the following four combinations in equal numbers:

Since RA, AR, and RR all give round seeds the Fa generation produces round seeds to angular seeds in the ratio of 3 : i . The two organisms with the gametic constitution RR and RA look alike, yet they are different in regard to heredity. The gametically pure form RR is called homozygous, the impure form RA heterozygous. 2. W. S. Sutton1 was the first to show that the behaviour of the chromosomes furnishes an adequate basis on which to account for Mendel's law of the segregation of the characters in the sex cells of the hybrids. If we disregard the cases of parthenogenesis and the X chromosomes, we may state that each

species is characterized by a definite number of chromosomes, e. g.1 In the fertilization of the egg the number of chromosomes is doubled (if we disregard for the moment the complication caused by the X and Y chromosomes which was considered in the previous chapter). It was noticed by Montgomery that each chromosome had a definite size and individuality, and he suggested that homologous chromosomes existed in sperm and egg and that in fertilization the homologous chromosomes of egg and sperm always joined and fused in the special stage designated as synapsis, which will interest us later. On the basis of this suggestion Sutton developed the chromosome theory of the mechanism of Mendelian heredity or segregation.

According to this theory, all the cells of an individual (inclusive of the egg cells and sperm cells) have two sets of homologous chromosomes, one from the father, the other from the mother. Before the egg and sperm are ready for the production of a new individual, each loses one set of homologous chromosomes in the sccalled reduction division, but the lost set is made up indiscriminately of maternal as well as paternal chromosomes, so that while one egg retains the maternal chromosome A the other will retain the paternal one, and so on. If before the reduction division all the eggs had the chromosome constitution A A If BB^ CClt DD^ (where A B C D are the paternal and A x Bt CL Z>i the maternal chromosomes), after the reduction division each daughter cell has a full set of four chromosomes, but maternal and paternal mixed. Thus the one cell may have AB^CD,, the other A1B1C1D1 etc. This, according to Sutton, is the basis of the Mendelian heredity. Suppose the determiner of a certain character (violet colour of flower in the bean) is located in a chromosome A of this species. The homologous chromosome in beans with white colour may be designated as a. According to. the chromosome theory of Mendelian heredity a differs from A in one point, though this difference is probably only of a chemical character and not visible.

If an egg with A is fertilized by a pollen with a (or vice versa), after fertilization the chromosome constitution of the fertilized egg is A a. All the other homologous chromosomes are identical and therefore need not be considered. All the nuclei of the Ft generation have the chromosome constitution A a. All will form eggs and pollen with nuclei of the same chromosome constitution Aa, but all these sex cells will go through the maturation division before they are fertilized; and this reduction division leads to the existence of two kinds of eggs in equal numbers, one containing only the A, the other only the a chromosome; and the same happens in the pollen. When therefore the hybrids Fx are mated among themselves, the following four chromosome combinations will be produced:

Now this is exactly the ratio of Mendelian heredity in the F2 generation. The plant with the chromosome constitution A A will form violet flowers, those with the chromosome constitution A a will form pale violet flowers, and those with the chromosome constitution aa will form white flowers. The result would be expressed by the formula AA: Aa: aa which is the same as that given for any character in a Mendelian case. Thus the phenomena of germ cell division and of heredity are seen to have the same essential features viz., purity of units (chromosomes, characters) and the independent transmission of the same; while as a corollary it follows in each case that each of the two antago-

nistic units (chromosomes, characters) is contained by exactly half the gametes produced. It is obvious that Sutton by this idea did for heredity in general what McClung had done for sex determination or sex heredity, that is, he showed that the numerical results obtained in Mendeiian heredity can be accounted for on the basis that factors for hereditary characters are carried by definite chromosomes. The cytological basis of sex determination becomes only a special case of the cytological basis of Mendeiian heredity. In the examples quoted the plants giving rise to violet and to white flowers are homozygous for the colour of flower having the chromosome constitution A A and aa respectively; while the plants with pale violet flowers are heterozygous, having the chromosome constitution A a in their nuclei. The former give rise to identical sex cells A and A or a and a; while the heterozygous plants give rise to different sex cells A and a.

From this point of view in Drosophila (and very probably also in man) the female is homozygous for sex having in all its cells the critical chromosome constitution XX and giving rise to one type of eggs only, each with one X chromosome; while the male in these forms is heterozygous for sex having in all its cells the chromosome constitution XY and forming two different types of spermatozoa in equal numbers X and Y. In Abraxas and in the fowl the female is heterozygous for sex and the male homozygous.

3. If the chromosomes are the vehicle for Mendelian heredity it should be possible to show that the various hereditary characters which follow Mendel's law must be distributed over the various chromosomes; and it should be possible to find out which characters are contained in the same chromosome. It has already been stated that sex-linked heredity is intelligible on the assumption that the X chromosome carries the sexlinked characters. T. H. Morgan and his pupils have shown with the greatest degree of probability that corresponding linkages occur in the other chromosomes and that there are irj Drosophila exactly as many groups of linkage as there are different chromosomes, namely four. x

Mendel had found that when he crossed two species of peas differing in regard to two pairs of characters, he obtained in the F2 generation results which he calculated on the assumption that the segregation of the two pairs of characters in the sex cells of the hybrids took place independently of each other. To illustrate by an example: When crossing a yellow round pea with a green wrinkled variety in which the characters round and yellow are dominant, green and wrinkled recessive, all the hybrids of the Fx generation had the

characters round and yellow. When these were inbred the Fa generation produced four types of seed in the ratio 9:3:3:1, namely: The explanation according to Mendel's theory is as follows: Since the segregation of each pair of characters occurs independently, there must be 3 yellow to I green and also 3 round to I wrinkled in the F2 generation. The yellow will, therefore, be round and wrinkled in the ratio of 3 : 1, which will give 9 yellow round to 3 yellow wrinkled. The green will also be round and wrinkled in the ratio of 3 : 1 , which will give 3 green round to I green wrinkled, which is the ratio of 9 : 3: 3: I found by Mendel.

On the basis of the chromosome theory the following explanation could be given of this numerical relation. The peas with yellow round seeds have sex cells with a factor for both yellow and for round in two different chromosomes; these two different chromosomes we will designate with Y and R. The peas with green and wrinkled seeds will have in their sex cells factors for these characters in two homologous chromosomes g and w, where g is the homologue of Y and w of R. The cells of the hybrids of the F, generation will have

the chromosome constitution Yg Rw, where, Y and g and R and w are homologous chromosomes which will lie Alongside each other ™. In the formation of sex cells a reduction of these four chromosomes to two takes place whereby, according to the theory of Button, the following two types of separation can take place: YR and gw, or gR and Yw. (A separation into Yg and Rw is impossible since the division takes place only between homologous chromosomes.) Hence there will be four types of eggs, YR, gw, gR, and Yw and the same four types of pollen cells. The F2 generation will produce the sixteen possible combinations in equal numbers: namely,

Since wand g are recessives and therefore disappear when in combination with their respective dominants Y and R the result will be 9 YR (yellow round), 3 Yw (yellow wrinkled), 3 Rg (round green), and I gw (green wrinkled) as Mendel actually observed and as all investigators since have confirmed. Bateson made the discovery that these Mendelian ratios 9:3:3: I did not always occur when forms differing in two characters were crossed. He found typical and very constant deviations from this ratio

in definite cases and these cases he interpreted as being due to "gametic coupling." These phenomena demonstrate the existence of a complex interrelation between the factorial units. This interrelation is such that certain combinations between factors may be more frequent than others. The circumstances in which this interrelation is developed and takes effect we cannot as yet distinguish, still less can we offer with confidence any positive conception as to the mode in which it is exerted.

Morgan has given an ingenious explanation of these deviations on the basis of the chromosome theory of Mendelian heredity. He assumes that they occur in those cases where the two or more characters are contained in the same chromosome. In that case the two factors lying in the same chromosome should generally be found together. Such was the case for instance in the experiments with flies having red eyes and yellow body colour versus white eyes and grey body colour, the character for white eyes and yellow body being located in the X chromosome (see preceding chapter), or in the experiments on Abraxas. These phenomena are called linkage, and the numerical results of linkage were given in the preceding chapter in connection with the crossing of sex-linked characters.

We have already mentioned that before the maturation division occurs the homologous maternal and paternal chromosomes fuse — the so-called synapsis of the cytologists — and afterward separate again. It had been observed by Janssens that in this stage of fusion and subsequent separation a partial twisting and a partial exchange between two chromosomes may take place. Morgan assumes that this exchange accounts for certain deviations in the ratio of link-

age. If in Fig. 40 the white and black signify two homologous chromosomes I and I x containing the two pairs of homologous factors AB and ab respectively, the synapsis state would be as in Fig. 41. If the separation were complete, either I or its homologue Ix might be lost in the maturation division of the egg. If, however, the synapsis is slightly irregular, as in Fig. 42, where the chromosomes are slightly twisted, I and I, will not separate completely but an exchange

will take place, part of It and I becoming exchanged. This would result in the formation of two mixed chromosomes Ab and aB (Fig. 42). This partial exchange of homologous chromosomes, which Morgan calls "crossing over," occurs, as he found in Drosophila, in the egg only, not in the maturation division of the sperm. He informs me that in the silkworm moth Tanaka found that it occurs only in the male, while in Primula it takes place both in the ovules and in the pollen as shown by (Gregory.

Morgan and his fellow-workers have put this theory to numerous tests by breeding experiments and the results have fully supported it. According to the chromosome theory linkage should occur only when factors lie in the same chromosome. Hence it should be possible, on the basis of this linkage theory, to foretell how many linkage groups there may occur in a species; namely, as many as there are chromosomes. In Drosophila there are four pairs of chromosomes, and Morgan and his fellow-workers found only four groups of linked characters. x This agreement can be no mere accident.