Book - Manual of Human Embryology 9

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   Manual of Human Embryology I 1910: The Germ Cells | Fertilization | Segmentation | First Primitive Segment | Gastrulation | External Form | Placenta | Human Embryo and Fetus Age | Ovum Pathology | Integument | Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | Figures | Manual of Human Embryology 1 | Manual of Human Embryology 2 | Franz Keibel | Franklin Mall | Embryology History

Mall FP. IX. The pathology of the human ovum in Keibel F. and Mall FP. Manual of Human Embryology I. (1910) J. B. Lippincott Company, Philadelphia.

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IX. The Pathology of the Human Ovum

Franklin Mall (1862-1917)

By Franklin P. Mall of Baltimore.

A large percentage of human ova that are obtained by embryologists are quite unlike the normal ones and therefore they need special study. From comparative embryology we have learned that in normal development the tissues are transparent and sharply defined, and that the organs of the embryo and its membranes maintain constant proportions in each stage of development. Any marked variations from these constants, which are as yet not well established, are to be viewed as anomalies, but if they are accompanied by distinctive tissue change of a pathological nature we view the ovum containing them as diseased or pathological. When the pathological processes of the ovum are pronounced the villi are atrophied and irregular; the chorion is thin and transparent, or thick and hemorrhagic; the embryo is usually dwarfed in an irregular fashion; the exoccelom is often filled with an excessive amount of dense reticular magma; and there is usually hydramnios with a granular deposit in the liquor amnii. These are the chief changes which are easily seen by a superficial observation of a pathological ovum, and since all of the changes are relative their recognition depends absolutely upon a knowledge of the normal form and relation of the structures within the ovum.

Seventy-five years ago Granville made a report of forty-five aborted ova, a few of them having complete histories, in which he concludes that the chorion is first diseased and that this in turn results in retarding the growth of the embryo. He also notes that an inflammatory condition must have been present in the uterus, for the abortion of pathological ova is usually accompanied with great pain and excess of bleeding. For the present I shall not consider the etiology of pathological ova, reserving this question for the conclusion of the chapter.

It is well known that the larger number of abortions occur during the second and third months of pregnancy, and according to Hegar there is one abortion in the early months of pregnancy for every eight or ten births at term. "A conservative estimate indicates that every fifth or sixth pregnancy in private practice ends in abortion, and that this percentage would be increased considerably were the very early cases taken into account, in which there is a profuse loss of blood following the retardation of the menstrual period for a few weeks" (Williams). Fully twenty per cent., then, of all pregnancies end in abortion and but 80 per cent, continue to full term.

Only a portion of aborted ova contain normal embryos which, judging by their state of preservation, were alive a short time before they were expelled. according to His, embryos which are slightly malformed, that is, young monsters, are occasionally seen, and their condition shows that they were living at the time of the abortion. His further states that he observed two specimens of spina bifida, several of anencephaly, one of ectopia of the liver, and one of cleft palate in ova that were sent to him in the course of several years. I have had a similar experience. By far the largest percentage of the specimens, however, contain embryos to which His applies the collective term abortive forms, characterized by a general arrest of development. His also noted that among the embryos sent him by his colleagues 22 per cent, were pathological, while in those sent him by midwives it rose to 40 per cent. In the first group there had been some selection in the specimens. My own experience, as well as that of Giaccmini, is similar to that of His, for physicians have a tendency to send good specimens only, and therefore we are of the opinion that the correct percentage of pathological ova among early abortions is considerably higher than indicated by His's statistics. My own records include 434 specimens (Nos. 1 to 404 in my catalogue) of all ages, among which there are 163 pathological ova and embryos of various ages. Among them there are 151 normal and 138 pathological embryos of the first two months of pregnancy, that is, in embryos less than 32 mm. long. Tor the sake of comparison I have arranged my data in chronological series parallel with those given by His.

Keibel Mall Pathology-table1.jpg

It may be noted that the percentage of pathological embryos in my first series is much less than in the subsequent series, a diflference similar to that found by His in his two series. At first, before 1898, there was also a tendency for physicians to send me the normal specimens, but since then I have repeatedly urged them to send me all specimens, and during the past ten years the pathological ova of the first two months of pregnancy have been about 50 per cent. These data are sufficiently good to be considered representative for America — especially Baltimore. It may be, and I think it will probably prove to be, that the percentage of pathological embryos will vary markedly in different communities and in different classes of society, to correspond with the frequency of uterine troubles as well as with the tendency towards sterility.

My own statistics show also that there are about twice as many pathological ova in abortions of the first month as are found in those of the second month. The statistics arranged in two groups are as follows :

Keibel Mall Pathology-table2.jpg

In the first month the low percentage of pathological ova, in Nos. 1-208, is due to the fact that no effort was made to collect them before No. 127. Up to No. 127 the percentage of the pathological is 44, but between Nos. 127 and 404 it has been constantly above 70. The figures and percentages for the second series (Nos. 209 to 404) are, therefore, representative. according to Marchand 615 monsters were found among 81,187 births, and these figures with the data I have just given enable me to give the probable number and percentage of abortions and of monsters found in every 100,000 pregnancies.

Pregnancies Births Nonnal embryos aborted Pathological ova aborted Monsters born at term
Number 100,000 80,572 11,765 7,048 615
Percentage 100 80 12 7 0.6

The above table has been constructed from Williams's statistics regarding the frequency of abortion, from Marchand's on births and monsters, and from the percentage (38) of pathological ova and embryos I have found among 434 abortions. This table permits the following statement. Eighty out of 100 pregnancies end in the birth of normal individuals; seven are aborted as pathological ova containing radical changes within them ; and about one (0.6) produces a monster at term. The remaining twelve ** normal" fetuses and embryos are by no means all normal, for we are constantly finding in them, especially the younger specimens, minor changes which must be viewed as forerunners to real monsters. Teratology will not be on a satisfactory scientific basis until many embryos with minor changes have been studied with as much care as Fischel has recently studied several yoimg embryos with spina bifida, and until the norm has been established with greater precision for every stage of development.

The line of demarcation between normal and pathological embryos is by no means sharply defined ; in all probability a number of the so-called normal embryos are slightly deformed or abnormal and we must continue to sharpen our conceptions of the norm. Even those specimens that are obtained directly from the uterus in operations or in autopsies are by no means necessarily normal, for a large percentage of all pregnancies contain pathological ova. The probabilities in favor of monstrous embryos is even greater in tubal pregnancies ; and we should be most cautious in declaring embryos obtained from them normal, even if they are well formed and are transparent and alive when they come into our hands. In passing judgment upon any given specimen we must continue to rely upon its comparison with well-known embryos of record, as well as with the structure of other mammalian embryos. Any deviation from the norm as thus determined should be viewed with grave suspicion, for it is likely to be pathological in nature.

His has pointed out that the state of preservation of an embryo is of much value in determining whether it was alive or not at the time of abortion. An embryo which is suflSciently transparent, or still translucent enough, so that the blood-vessels and other structures within can be recognized, was probably alive shortly before or at the time of abortion. Such an embryo is also probably normal. When they are hardened in formalin or other suitable preservatives their external contour is in beautiful even curves, and their sections show the boundaries of the organs and the histological details sharply defined. These conditions, however, only indicate that a specimen is in all probability normal. There is always the possibility that an embryonic monster with but slight changes has been aborted early in the pregnancy, and as more young embryos are studied we find the percentage of them is larger than we anticipated.

Poorly preserved specimens, that is, those which show signs of maceration before they were fixed, are not necessarily pathological; their condition may be due to post-mortem changes, either before or after the abortion. In case their death took place within the uterus a certain number of them may show changes in the amnion and chorion, but even in these cases we are not necessarily dealing with abnormal embryos. Abnormal conditions of the uterus may kill a normal embryo without causing it to become monstrous or to abort. In fact, it seems to be quite common for the act of abortion to extend itself over a number of days, and if such abortions are due to the death of the embryo it is natural that it should undergo some maceration before it is born.

These views, given almost verbatim from His, are now quite generally entertained; but I think it likely that he emphasized too much the early and complete death of the embryo before the abortion. At the time he first wrote upon this subject he believed that the primary cause which produced pathological ova lay in either the germ or the sperm before fertilization, but in his last contribution to this subject he expressed himself in favor of the view that the changes in pathological ova are of a secondary nature due to external influence. In fact, recent work in experimental teratology, as well as my own studies of pathological human embryos, bears out this view. In this chapter hereditary malformations, like Polydactyly and muscle anomalies, are not considered. Pathological embryos, experimental monsters, and human monsters at term form a class by themselves, inasmuch as they are produced from normal ova through causes which lie in their environment.

Embryos that die suddenly are usually aborted at once, and if they are not they macerate and disintegrate but do not continue to grow in an irregular fashion as do pathological embryos. The latter become rounded, grow into nodules or into cylindrical forms, but do not die immediately. Judging by the well-preserved state of the tissues so frequently encountered, especially the epidermis, I am inclined to the belief that they lived up to the time of the abortion. However, viewed with the naked eye, the embryo is usually opaque,^ the borders of the internal organs are quite obscure, and no bloodvessels are seen through the skin. Furthermore, the sharp outlines of the branchial arches, head, hands, and feet are often wanting; the embryo is not dead, but has grown in an irregular way, just as do fish, frog, and bird embryos when experimented upon. Not only are the protruding parts of the embryo atrophic, but the tissues do not move with sufficient rapidity to bring about the proper form of the subsequent stage, thus producing all kinds of arrestments of development, for example, spina bifida, anencephaly, and cleft palate. In other words, monsters of all varieties and of all degrees of intensity are produced in the first months of pregnancy. As a rule, the changes in them are so radical that they lead to their own destruction and they are aborted. according to the table given above twelve monsters are aborted for each one that develops to the end of a normal pregnancy.

There are, however, other characteristics of pathological ova that are more recognizable to the naked eye than are those of the embryo. The most apparent of these is the diminished size of the embryo, first described by His (Fig. 149). In order to make this statement it is necessary to determine the relative size of the embryo and chorion in different stages of development. The figures of His, which are given in the first two columns of the following table, show that the length of the embryo is about onefifth of the diameter of the ovum in younger stages and one-third in older ones.

The measurements of the chorion include the villi, which may add somewhat to the great amount of variation in the different colmnns. I think It would have been better if the villi had not been included, for they are also a variable quantity, especially in pathological ova.

In the table I have placed after His's figures my own for both normal and pathological ova. It will be noticed that my probable deviations vary considerably more than those of His, while the extremes do so still more. In fact the probable deviation is so great that only in extreme cases is the ratio of the length of the embryo to the diameter of the chorion of any value in determining whether or not the embryo is pathological. However, the measurements of the pathological embryos in general are less than those of the normal, especially in the larger ova. In a few instances the embryos

Fig. 150. — Ovum containing a deformed embryo 5 mm long.

embw s mm. loos. are larger than the normal, which really should be interpreted the other way round, i.e., the chorion is too small for the embryo and is markedly fibrous, while the embryo is nearly normal. Only in the extreme cases, therefore, are "embryos 4-5 mm. long found in chorions 4.5-5 cm. in diameter, or embryos 2.5 mm. long in chorions 3.5-4 cm. in diameter " (His).

His also pointed out that pathological ova containing small monsters usually have marked hydramnios. In normal development the amnion hugs the embryo quite closely until the beginning of the sixth week, when its cavity enlarges more rapidly than the embryo, and by the beginning of the third month of pregnancy grows to obliterate the exoccelom. In pathological ova, however, large dilated amnions are found containing small atrophic embryos. In other words, hydramnios is frequently found, just as is the case when experimental terata are produced in hens' eggs. AH of this speaks decidedly against the prevailing amniotic theory of the cause of monsters, which is dependent upon hypothetical amniotic bands and contraction of the amnion early in development. In addition to the hydramnios found so frequently in pathological ova the walls of the chorion are often very thin and transparent (Fig 150), or thick and hemorrhagic (Fig 151) ; and the villi, which are unequally and poorly developed, are scattered over the chorion in an irregular manner (Fig 152). In such ova the villi are sometimes arranged in small groups forming islands, between which there are large bare spaces composed of the main wall of the chorion only (Fig. 155).

In normal development the exoccelom is filled with a mass of delicate fibrils which bind the amnion to the chorion. These fibrils, which do not seem to be connected with cells, give the fluid of the exocoelom a jelly-like consistency and form the main part of the magma reticule of the older anthers. As the amnion advances and encroaches upon the coelom the fibrils of the magma gradually form in a layer which finally rests between the amnion and chorion after the exoccelom is obliterated. A second group of pathological ova in which there is no hydramnios often have their exocceloms stuffed with magma reticule, and Giaccmini has shown that its excessive development always indicates that the ovnm is pathological. My own experience fully confirms that of Giaccmini.

Keibel Mall 151.jpg

Fig. 151. — Section of a hemorrhagic chorion with the adjacent yolk sack. The deformed embryo was 4.5 mm. long. The walls of the umbilical vesicle contain many blood-vessels which communicate directly with those of the chorion.

All stages of an excessive development of the magma are seen, from those in which the fibrils are but slightly accentuated to those in which they form a dense hyaline mass (Figs. 153 and 154). In many respects the fibrils look much like those of flbrin, hut they do not give Weigert's fibrin reaction. As the magma grows and becomes more fibrous it also often undergoes a granular degeneration (Figs. 156 and 157), and pathological magmas are therefore of two varieties, which 1 have termed reticular and granular respectively. Nor is the magma always confined to the exoccelom in pathological ova; it may also penetrate the amnion and more or less fill its cavity (Fig. 160). However, this is rare in the ease of reticular magma, that within the amnion being nearly always granular in nature (Fig. 161). In pathological ova irregularities in development may be seen. The magma may become too extensive, the amnion may grow too rapidly, or in relation to the growth of the chorion the embryo's development may be retarded. The changes are no doubt due to retarded development of some portions of the ovum rather than to death of the entire structure.

It was mentioned above that His gradually became convinced that pathological embryos were due to secondary changes in embryos which had been normal, a view advanced long before by Granville. He came to this conclusion on account of his study of the structure of pathological embryos which showed abnormal changes in suCoessive stages of development. Were the difficulty germinal in origin these changes should be suCoessive from the smallest to the largest pathological embryos, and they should not arise from various stages of normal embryos (Figs. 162 and 163). The real condition of things pointed towards the environment of the ovum and not to the germ for the cause of the abnormality. It was difificult for His to come to this conclusion, because at first he was of the opinion that ordinary monsters in the narrower sense are due to primary changes in the germ.

Keibel Mall 162.jpgKeibel Mall 163.jpg Keibel Mall 164.jpgKeibel Mall 165.jpg

His did not examine the membranes of his specimens microscopically, but he has repeatedly referred to changes in the chorion of pathological ova which are recognizable with the naked eye. In fact, if special care is not taken in the examination of the chorion of these specimens, one is often inclined to think they are normal, and this error has been committed by both Giaeomini and myself. However, triaccmini recognized that in some instances the chorion is not altogether normal in structure, which he thought might be due to secondary changes after the death of the ovum, either before or after the abortion. In my own case I was gradually led to believe that there were two classes of pathological ova, one in which the primary trouble is in the chorion, and the other in the embryo. In the first group the embryo is dwarfed and in the second it is destroyed altogether. This conclusion was based upon anatomical study, for in the first group the chorion is usually pathological and in the second it often appears to be normal. However, more recent studies, with better material than I had at first, show an ever-increasing number of pathological membranes in both groups (Figs. 165-168), and I think that this classification of pathological ova must be abandoned. It appears now that the membranes of nearly all pathological ova are pathological, and, what is more, the deeidua, syncytium, and chorion are frequently affected in specimens containing apparently normal embryos. The borderline specimens can not be considered satisfactorily at present because they have not been investigated sufficiently. My more recent investigation of this question shows that the chorion is diseased in 113 out of 132 pathological specimens studied. The nineteen in ■ra«m. rttimw, »ithm which there which the chorion is said to be normal kcu agio r . show changes in the decidua in a few cases, and the rest are mostly older specimens before formalin was used. Fifteen of them are ova without embryos, that is, specimens in which the embryonic mass was destroyed at a very early date. In some of these the chorion and deeidua are undoubtedly normal in every respect. A specimen 6 mm. in diameter, which had been scraped out of the uterus on account of chronic endometritis, was perfectly developed, the decidua, syncytium, and villi being normal ; but it contained no embryo and the Coelom. was filled with magma reticule and strands of mesoderm cells from the chorion (Fig. 1G9). But to this case there is a history of uterine trouble which may have been of sufficient importance to affect the embryo at a very early stage in its development. Comparative experimental ter.atology supports this view. The distribution of the specimens into normal and pathological chorions is given on page 224 with the table on the distribution of the embryos. It shows that in all but a few cases in which the embryo was present the membranes were also pathological.

Fig. 155. Photograph of an ovum 50x30x30 mm covered with irregular villi.

The changes in the chorion may now be briefly given. The most common of all is a fibrous degeneration. The mesoderm, instead of being beautifully transparent and of even structure, becomes coarse and fibrous, with the nuclei closely packed together. There may be atrophy or hypertrophy of the villi, as well as of the main wall of the chorion. Next we have (edematous, mucoid and hyaline changes in the villi, in which there is a tendency to destroy their structure; in these there are also often vacuoles and larger spaces containing granules. These changes may be found in villi side by side with others that are normal, showing that the chorion may have both destructive and constructive changes going on in it at the same time. in tact within the magma of Uiecnumihown in tli ise this must also be the case in normal development, but until the norm of the growing chorion is established very little can be said about this process. In the present state of our knowledge pathological changes in the chorion must be very marked in order to be recognisable.

Fig. 156. "Shadow" of an embryo 3.5 mm long lying within the magma of the ovum shown in Fig 155.
Fig. 157. Piece of an ovum (18x14x14 mm) showing a large clump of magma in the coelom.

In many pathological ova the blood-vessels of the chorion undergo degeneration long before the embryo becomes necrotic, as may be seen from the discussion of this question in my large monograph. Or blood-vessels may be present after the embryo is destroyed entirely. At first I was inclined to think that in this latter instance it was necessary to assume the presence at one time of an embryo nearly 2 mm. long, for at this time the vessels grow from the embryo to the chorion in normal development. Recently I have observed the growth of blood-vessels, in several specimens, passing directly from the yolk sack to the chorion, which proves that it is unnecessary for the body of the embryo to develop in these cases (Fig. 170).

The chorion also shows all kinds of changes of its syncytium. It is often deficient, irregular, or necrotic, or intermixed with leucocytes, which may form small abscesses in it. In some instances, which are not rare, both syncytial cells and leucocytes invade the mesoderm of the chorion, and thereby hasten its destniction. The changes in the decidua are harder to follow, because it rarely remains attached to the chorion and is usually lost. However, in some instances it was found infiltrated with leucocytes, often in large groups, when the rest of the chorion appears to be normal. Above all, this structure is in need of much more careful study than it has received before the chain of evidence of pathological ova is complete. However, one point is certain, disease of the chorion is as common as are pathological embryos, and the two usually coincide.

In nearly all of the pathological ova a peculiar stringy substance dotted with numerous very fine granules is seen between the villi (Fig. 171). This fibrinous or mucoid mass extends between the villi after covering their tips. Within it numerous leucocytes are frequently seen (Fig. 174), and into it nests of syncytium often grow. However, the latter do not radiate and spread ittimu within [he amniQii. instead they form clumps or rounded ends at the tips of long strands of cells. It appears as if they fail to receive their proper nutrition from this substance, which is no doubt pathological in its origin. The constancy of mucoid substance in pathological ova and the general relations of the tissues which come in contact with it makes of it a valuable sign of the pathological state. It is of especial value for this purpose, as it is present in the earliest pathological specimens before any other marked changes have taken place in tlie walls of the chorion (Figs. 175 and 176).

Keibel Mall 158.jpg

Fig. 158. — Section of the chorion of Fig 157, showing a large nest of syncitium invading its wall.

Keibel Mall 159.jpg

Fig. 159. — Section of the villus of the ovum shown in Fig. 157. S - syncytium

Fig. 160.— Ovum containing a "normal embryo" 20 mm long with considerable magma reticule within the amnion.

Keibel Mall 161.jpg

Fig. 161.— Ovum 50 mm. in diameter with the embryo incrusted in granular magma.

Pathological embryos were first classified by Panum in his experimental study of early monsters in the hen's egg. This classification is used as a basis by His for pathological human embryos and therefore will be given in full. Panum found that there were two great groups of monsters: (I) those in which the whole embryo is involved, and (II) those in which but a part of it is affected. Under the first group there are the following subdivisions: (1) flattened forms with the production of red blood, that is, the embryo only is affected ; (3) cylindrical forms, the embryo becoming abnormal later in its development; and (4) amorphous forms. The forms brought together by Panum under the first group (I) correspond in many respects to those described by His in his classification. Among them His found three main groups of pathological embryos: (1) nodular forms, in which the embryo is largely destroyed leaving but a small mass of tissue; (2) atrophic forms, in which the embryo is more or less distorted; and (3) cylindrical forms, older embryos than those classed under (2),in which the head has usually suffered most by the pathological process. It is easy to see the similarity between the cylindrical forms of Panum and His in chicks and in human embryos; in both it appears as if the pathological process began quite late in development. Amorphous forms can be compared with the nodular forms of His ; in both cases the pathological process began quite early in development and produced radical changes in the body of the embryo. His's atrophic, abortive, or degenerative forms are composed generally of small embryos, younger than the cylindrical forms and older than the nodular forms.

His did not recognize a class in which the embryo is destroyed entirely {Panum's class II, 2), for he had never seen a human ovum without an embryo. However, such specimens are not rare ; Giaccmini has described a number of them, and I have found many more. So in Giaccmini 's classification there are two main groups : (I) those in which the embryo is missing, and (II) those in which the embryo is present, but deformed. Under tlie second group he recognizes His's nodular and atrophic forms. In the first group he classes the ova according to the presence or the absence of an amnion, and he also gives a third group which presupposes that the embryo has the power to wander and migrates through the cavities of the ovum or out of it entirely. I consider this group unnecessary and fantastic; it includes ova in which the embryo has been displaced by mechanical means.

Keibel Mall 166.jpg

Fig. 166.— Section of a villus from an ovum 100x50x40 mm, containing an embryo 60 mm long. V., villi; N., necrotic villus and syncytium; H., hyaline degeneration of the mesoderm and syncytium; X., peculiar masses of cells in the mesoderm, probably degenerating blood-vessels.

Keibel Mall 167.jpg

Fig. 167.— Ovum (10x7x5 mm) from a tubal pregnancy. Some of the villi are degenerated, others are nearly normal and contain blood-vessels, but no trace of the embryo could be found within.

Keibel Mall 168.jpg

Fig. 168.— Section of a villus from an ovum 35x25x15 mm. Large groups of syncytial cells, S, are invading the mesoderm.

Keibel Mall 169.jpg

Fig. 169. — Section of a villus tram an ovum of 35 X 2G X 15 nun.

Keibel Mall 170.jpg

Fig. 170. — Section of ths chorion vith alruida of mesenchyme »1Ib i mm. in diunetcr. M.. Heeenohyme odl>: CA., mil of tbe chorioD; £.. nei the remnmnt of (he embryo.

Lastly, I give my own classification in the form of a table in which the data are arranged with those of His, giving the number and percentage of specimens under each heading. It is noticed

Keibel Mall 171.jpg

Fig. 171. — Section of llie chorionio nail o( bq ovum ot 16 X 7 >< 6mm. D.. decidus; 8„ ayDoytiuini V., that the percentage is nearly the same in each collection when the figures are arranged in parallel columns. I always considered it remarkable that His never observed an ovum without an embryo, for 28 per cent, of my specimens are of that kind. However, many of them are bloody or fleshy moles, while others are ova which appeared to be perfectly normal until they had been cut into serial sections. I have also compared my vesicular forms with His's nodular forms, for no doubt they are the same in most cases.

Keibel Mall 172.jpg

Fig. 172. — Photograph ot an embryo

•This Dumber locludei some of my speclmem ol the teTcath week,— i.e., kll embryo* len than 15 mm. long.

His did not cut sections of the nodular forms, and had he done so he would probably have found them, as I did, often composed of a single umbilical vesicle without an embryo, which "Was frequently not attached to the chorion. The large percentage <12) of vesicular forms in my collection is probably due to the refined method I have employed in examining these specimens, most of them having been cut into serial sections. Giaccmini notes especially that it is unnecessary to make a group to include the vesicular or cystic forms of pathological ova, for they may be scattered under the various headings of his classification. Under this Group I include those in which the entire embryo has been destroyed, leaving only the umbilical vesicle and sometimes a portion of the amnion. The remnants of the embryos of this group correspond well with Panum's II, 2, in which the embryo is destroyed but the area vasculosa remains and gives rise to blood, just as the vesicle in this form of human monster is composed mainly of an umbilical vesicle with its primary bloodvessels. It may be noted that some of these umbilical vesicles have been confused with the amnion in Giaccmini's fantastic group, in which the embryo has wandered out. It is further stated by Giaeomini tliat the openings through which the embryo wandered often healed up, for they could not be found.

Keibel Mall 174.jpg

Fig. 174. — Section of the decidua, villi, anf chorion of the specimen shown in Fig. 172. There is a mass of mucus between the villi which contains many leucocytes.

Table of Pathological Ova

In the next table I have arranged nearly all of my pathological ova under various headings, omitting only a few embryos over nine weeks old.

Group I. — In the first group are the vesicular forms in which the main remnant of the embryonic mass is composed of the umbilical vesicle (Figs. 176a-178). In some of them the amnion is formed and in others it is destroyed entirely.

Group II. — In the second group there is neither amnion, embrj'o, nor umbilical vesicle; only the chorion remains. This group must have formed from that variety of Group I in which there is no amnion present. Vesicular and solid moles may arise from this group.

Group III. — In this group the embryo was destroyed after the amnion had been formed; usually it lines the chorion. All stages of the complete destruction of the embryo are found in this group, from a necrotic, granular mass to a vesicular ovum lined by the amnion with but a very short stump of the umbilical cord left (Fig. 179).

Group IV. — The embryo is present in this group and is more or less degenerated. In case it is much degenerated it may produce a nodular embryo of His or an amorphous embryo of Panum. Usually after the fifth week it is quite easy to recognize the stage in which the embryo became pathological. The younger ones correspond with His's abortive, atrophic, or degenerated forms, the older ones often with his cylindrical forms (Figs. 180-183). I have found it more convenient to arrange them in weeks according to the age of the embryo at the time the pathological process began. The embryos of any given week may contain any of His's atrophic forms according to the extent, degree, and duration of the pathological process. It is noteworthy that there are so few pathological embryos of the fourth week in my collection, while relatively there are four times as many in His's collection. Just the opposite is the case with the vesicular or nodular forms. It may be that I have had a tendency to class with these embryos those that he classes with the nodular form. The vesicular forms are intermediate between ova without embryos and ova with pathological embrj'os of the fourth and fifth weeks.

Keibel Mall Pathology-table2.jpg

Keibel Mall 175.jpg

Fig. 175.

Keibel Mall 176.jpg

Fig. 176. — Seetion through the tipe of the viUi of tn oiTim M mm. Id dtametar. The embryo in. 2 mm. loag, is delanaed but nearlr iuiiiiibI. S^ Byiuvtium: K., villa*; F., fiacmeuted uuola; , necrotie synoytium.

Keibel Mall 177.jpg

Fig. 177. — Ovum

Keibel Mall 178.jpg

Fig. 178. — Section Ibrouifa the vesicle withio the ovum ebown in Fie. ITT. The double vnide ' 3.3 mm. The imoLker vende betwBflQ the larfer one And the chorion may bt the Ainniotio cavity or poagibly the dil«(«d kllkntoie, althmifh it ia not *tt««hed to the choriaa.

The largest number of pathological embryos are formed during the first seven weeks of pregnancy; their number falls off markedly in the eighth and ninth weeks ; and but very few occur after the tenth week. Pathological embryos that survive the second month will probably eontinue throngh the normal period of pregnancy and give birth to monsters. From statistics given above, this should be the case in every twelfth pathological ovum. Vol. I.— 15

Keibel Mall 181.jpg

Fig. 181. — Section

Keibel Mall 183.jpg

Fig. 183. — Section

It may also be suggested, with Giaccmini, that threatened abortion in early pregnancy should be encouraged, for the cause of it is probably a pathological ovum and the uterus should be relieved of it. Careful investigations should also be made in these cases regarding the cause of the primary trouble. Sterility, or tendency towards sterility of women, especially if it is acquired, should be studied much more carefully than it has been for the sake of scientific teratology and the scientific treatment of abortion. The study of pathological ova has shown tiiat the embryos within are deformed and that there are structural clianges in the chorion which appear to be associated with inflammatory processes in the uterus. The villi are usually fibrous or are otherwise degenerated, the syncytium is atrophic or necrotic, and there is an excess of blood and mucus rich in leucocytes between the villi. These are also often invaded by syncytial cells and leucocytes. The picture indicates that the chorion is affected by an inflamed uterus, which naturally interferes with its nutrition. It is probable, however, that the process is somewhat more complicated, for the trouble often seems to lie within the decidua, especially in tubal pregnancies, which nearly always contain pathologcal ova (Fig. 184). In such cases the inflammatorj-process around the chorion is not so marked, but the decidua is deficient and there is an excessive amount of blood between the villi {Pig. 170). In both cases the nutrition of the ovum is affected, in the uterus by inflammatory and in the tube by hemorrhagic processes, which interfere with its implantation. As a result of faulty implantation the chorion degenerates or its further growth is retarded and the embrj'O suffers and becomes atrophic.

On the other hand, it is also possible to view the change in the chorion as secondary, as a result of primary changes in the embryo which are germinal in origin. In fact this view of them is entertained by many pathologists, who would consider the ovum as a foreign body after the death of the embryo, and all of the inflammatory changes found within it as of a secondary origin, as would be produced by a sponge if it were put in its place. This second attitude, which considers the changes within the embryo and in the chorion as a coincidence, is, I believe, incorrect. To be sure, it is well known that a woman who aborts a pathological ovum or gives birth to a monster is more likely to do so again, and this is the great argument in favor of the theory that the primary trouble lies in the germ and not in its environment. However, if pathological ova and monsters are due to a diseased condition in the uterus which interferes with the implantation of the ovum, this fact speaks equally as well for the environmental as it does for the germinal theory. The facts bearing upon these two theories I shall give briefly and in the order of their value.

Keibel Mall 184.jpg

Fig. 184. — Section

1. It is shown in the table given in the beginning of this chapter that of all pregnancies 7 per cent, end in pathological ova. In case the pathological condition is present in either the germ or sperm that same percentage of pathological ova should be found in ectopic pregnancies. I have taken considerable trouble to investigate the evidence obtained from tubal pregnancies, and in general find stated in the literature that more deformed embryos are found in them than should be; but this statement is rather an opinion than a demonstration based upon actual records. The answer to the question is complicated and rendered difficult by the rupture of the tube, which is of frequent occurrence, through which the embryo is easily lost in case it was present. I have collected all the cases of unruptured tubal pregnancies from Dr. Kelly's gynaecological laboratoryand find that there are forty-six in which the tube has been examined by refined modem methods. The enlargement in the tube containing the ovum measured in these specimens from 1 to 6 cm. in diameter, and in thirty-nine of them remnants of the chorion were found with villi ramifying through the blood-clot. Five contained pathological embryos, and but two contained normal embryos which were of the second month. In these two the chorion was well implanted, having a well-formed decidua, as is usually the case in the uterus. In all the rest the villi were of irregular shape, usually atrophic and degenerate, sometimes very long and thin with much blood between them, and the decidua was irregular and scanty. In these the implantation was faulty, and as a result 96 per cent, instead of 7 per cent, became pathological or produced monsters. This is the strongest argument against the germinal theory.

2. Von Winckel has done us a great service in collecting the data regarding the condition of live fetuses which had been removed from ruptured ectopic pregnancies by surgical operations. They, of course, were derived from the 4 per cent, of normal embryos mentioned above, for the pathological changes in the 96 per cent, were so radical that they could not develop into fetuses of any kind. Von Winckel's specimens are especially valuable, inasmuch as they show the possible fate of the normal embryos I found in tubal pregnancies obtained from Dr. Kelly's clinic. Forty-seven out of eighty-seven fetuses were much deformed and twelve were markedly monstrous; but eight were really normal. Among the monsters there were six specimens of hydrocephalus, one each of hydromeningocele, spina bifida, encephalocele, anencephalus, omphalocele, and hypospadia. In addition, the head was deformed fifty-seven times, legs forty-four, and arms thirty-five, with club-feet in twelve and amniotic bands in four cases. The placenta was usually deformed, sometimes multiple and sometimes broad, thin, or short, and often very hemorrhagic. In general, the poles of the body suffer most, the head being deformed in 75 per cent., legs in 50 per cent., arms in 40 per cent., and the trunk in 4 per cent, of the cases. It is clear that the difficulty is due largely to ordinary mechanical causes which interfere with the growth of the placenta and the poles of the embryo and frequently produce typical monsters. From the data given, it is seen that but very few of the embryos in tubal pregnancies produce normal individuals.

3. Comparative experimental teratology has shown us that all varieties of monsters found in man can be produced in large numbers from normal ova after fertilization as well as from normal embryos. I can only enumerate the results, the literature and general discussion having been given in my larger monograph, as well as in Hertwig's **Handbuch."

a. Polysomatous monsters can be produced by a variety of mechanical methods from normal eggs. Thus Vejdowsky showed in 1892 that the number of monsters produced from Lumbricus eggs was greater in the summer months than in cool weather ; and somewhat later Driesch suCoeeded in producing monsters from sea-urchin eggs by separating the cells in the two-cell stage by mechanical means, or by increasing their temperature, which acted upon them in a similar way. Somewhat later Loeb produced double monsters from sea-urchin eggs by changing the chemical composition of their surrounding sea water. In case it is diluted its rapid absorption by the egg causes the cell membrane to rupture, through which some of the protoplasm often escapes; upon returning the egg to normal sea water segmentation begins, nuclei wander out into the extruded protoplasm, and a double monster develops.

These important discoveries were next extended to vertebrates by Wilson, who experimented upon AmpMoxxis; and then by 0. Schultze, who experimented upon frog eggs. Both teratologists used mechanical means to produce double monsters. Wilson shook his eggs after segmentation to form hour-glass shaped eggs, and Schultze fixed the eggs between two glass slides and inverted them after segmentation had begun. The partly separated blastomeres gave the anlagen for the bodies of the two embryos, and recently Spemann has produced double monsters in the frog by tying its eggs with a fine thread at the right time. Furthermore, Tornier has produced double legs or even clusters of legs from the single anlage of the leg. These experiments all show that polysomatous monsters are produced from normal eggs.

b. Another variety of monster, not well developed and polysomatous, but atrophic and merosomatous, is found in lithium larvae. In 1893 Herbst found that there was often an inversion of the blastodermic membranes in case developing sea-urchin eggs were subjected to the action of lithium salts. Morgan extended these experiments to frog eggs and found that the inversion of the layers was due to a failure of the upper protoplasmic contents of the egg to move downward, and he concludes that this arrest is due to the physical and chemical action of the lithium. These monsters are similar in appearance to the irregular nodular forms produced by Panum, Dareste, and Fere, and are interesting inasmuch as they show that the action of lithium upon a normal egg is specific; the lithium produced a definite action upon the egg, interfering with its internal growth and also with its nutrition.

c. It has also been shown by Loeb that the action of calcium salts upon eggs has a specific action upon the growth of the heart and blood-vessels, by preventing the heart beat and retarding the growth of the blood-vessels, as well as of the embryo in general. Although Loeb states expressly that the action of the calcium is specific, as the rest of the embryo remains normal, I am inclined to believe him in error regarding this point, because he did not examine his specimens microscopically and because Knower has recently shown that mechanical enucleation of the heart in young embryos is followed by the gravest consequences. In such embryos the pronephros becomes oedematous and the lymphand blood-vessels and body cavities become distended. There is a general arrest of development of the embryo; the coils of the intestine are atrophic and there is histolysis of the mesentery and vacuolation of the muscle cells. Teratologists recognized long ago that the heart must be affected more or less in monsters, on account of the frequent occurrence of an oedematous condition of the tissues, as well as of accumulation of fluid in the serous cavities and of the hydramnios and hydrocephalus. Such conditions are often seen in pathological embryos, as well as in the monstrous chicks which were produced experimentally by Panum and Dareste.

d. In 1892 Hertwig published his remarkable essay on spina bifida, which is of far-reaching importance. However, it was Morgan who discovered that spina bifida may be produced experimentally by subjecting frog eggs to the action of common salt. It was found that a 0.6 per cent, solution delays the development of the egg (the chorda, intestine, myotomes, and nervous system developing normally), but gastrulation is postponed for from twelve to twenty-four hours. Posterior spina bifida naturally results. Later in development the exposed cord undergoes cytolysis and histolysis. Subsequently Hertwig extended Morgan's sodiima experiment to axolotl. Here the reaction is sharper than in the frog and there is also often anencephaly. It was found that a 0.5 per cent, solution had no effect upon the embryo at all, a 0.6 per cent, solution made half of them monsters, and in a 0.7 per cent, solution all of them developed spina bifida. Schaper has removed the brains of tadpoles mechanically* and Harrison has done the same with the spinal cord. In these experiments the embryo grows normally without spinal nerves or cord unless the operation destroys the lymph hearts also ; then dropsy follows. In fact this seems to be always the case when the heart is involved by either mechanical or chemical means.

e. The great precision by which spina bifida is produced by the action of sodium salts is equalled in a more striking manner by Stockard's magnesium experiments, in which typical cyclopia is produced in 50 per cent, of the fishes {Fundidus) experimented upon. Teratologists have speculated upon the cause and the development of cyclopia for centuries, and now with one stroke all is clear. Ten years ago Born occasionally produced cyclopia by splitting the head of the embryo through its sagittal plane. Later Spemann produced the same by ligature of the head, and Levj' by cutting off the front tip of the head. Harrison also often produced a new variety of cyclopia by removing the brain of the embryo; the eyes then wandered to the back of the head in the region of the pineal eye and appeared to unite. By a very different method Lewis suCoeeded in producing cyclopia in a large percentage of the specimens experimented upon. He pricked the extreme end of the embryonic shield of Fundulus and from such eggs embryos with all degrees of typical cyclopia developed. Of course, the striking experiment is Stockard's, and recently he has given an account of the anatomy of his embryos. At any rate, all these experiments show that all kinds of monsters, including spina bifida and cyclopia, are produced from normal embryos due to external influences.

4. The consensus of opinion of gynaecologists is that pathological ova are due to a diseased uterus, but they are not inclined, to associate pathological embryos with monsters. Neither do they speak of curing the uterus of women who have given birth to monsters in order to prevent them from doing so again. However, the evidence I have given above proves that monsters are produced from normal eggs by conditions which either interfere with their nutrition or poison them, and that in tubal pregnancies there is a great excess of pathological ova and monsters. How is it with pathological ova which come from the uterus! Is the uterus usually normal, or pathological! The chorion in nearly all pathological ova examined shows signs of inflammation, often severe, which is, of course, uterine in origin. Taking all of the pathological ova in my collection, thirtythree altogether, in which any data regarding the women from whom they were obtained are given, it is found that they are easily arranged in three groups.

(1) In the first group of eleven cases the main trouble preceding the abortion was a severe hemorrhage extending over a number of days.

(2) The second group of twelve specimens were abortions from first pregnancies in newly married women or relatively sterile women who had been married for some time and were anxious to have children.

(3) The third group of ten specimens were from women who had given birth to a number of healthy children and then began to abort, often a second or a third time.

The first group throws no light upon the question we are discussing, but the second is of value because it comes from sterile women. The third group is more easily explained. The women, perfectly healthy at first, gave birth to one or more children and then conceived and aborted quite regularly. In these cases the uterus was normal at first, but later, due to a variety of infections, became inflamed, and thereafter the fertilized ovum could not implant itself, became pathological, and was aborted. My records also state that seven of the women are healthy and twelve have uterine disease. In general, those with uterine disease belong to the second and third classes mentioned above. It may be noted that all the pathological conditions of the ova of the third group could not be due to germinal causes, for all these women had given birth to healthy children and the probabilities for any class are but 1 to 14. The data only confirm those obtained from tubal pregnancy, as well as those from experimental teratology, that is, the primary cause is in the environment.

5. Especially interesting are those cases in which two pathological embryos are obtained from the same woman. Five such sets are in my collection, and in four of them the changes in those of a set are alike. Two sets are duplicate twins and one is composed of two twin ova from a woman who had aborted before. The fourth set are about a year apart from a woman who had had nine children, after which her health failed (ten years Bgo) ; since then she has conceived regularly and aborted every time. The chorions of these two specimens are well infiltrated with leucocytes, the villi are largely destroyed, and the changes in the two embryos are severe and much alike. The fifth specimens are from a young woman, mother of two children, and the first of these appeared normal with the exception of an excessive amount of granular magma in the amnion, with leucocytic infiltration of the placenta. Nine months later a second typical pathological embryo was obtained from the same woman. Disease of the uterus began with the birth of the second child. Later she aborted again. Although these cases do not prove the point made they at least indicate that the same environment affected the ova of either suCoessive or twin pregnancies in the same way.

The theory that merosomatous monsters are produced by mechanical influences was established by Lemery, defended by the Saint-Hilaires, but was antagonized to the utmost by Meckel, Bischoff, and others. In case they are produced from normal embryos by means of external influences it follows that the embryo must become wholly or in part diseased or pathological, a view entertained by Morgagni. Frequently the pathological changes in the fetus were compared with those in the adult and it was believed that they were also due to a variety of diseases, such as syphilis, tuberculosis, rickets, or to inflammation. However, it was impossible to show that the destruction of tissue necessary to produce a monster was associated with pathological changes peculiar to these diseases, but instead they nearly always appeared to be normal in character. Panum defended the nosological theory and asserted, with good reason, that only the fundamental characters of the changes within the embryo in a given disease should be like those in the adult. In fact he asserted that the nomenclature for the pathological changes in the embryo cannot be the same as that for the adult, and this opinion is borne out by the numerous investigations during the last fifty years. At best, Panum states, the etiological factors are the same for diseases of the embryo and of the adult. He had found in experimental chick monsters due to malnutrition that there are constant tissue changes, such as will produce exudates, bring about adhesions, and cause atrophy with scar formation. And since these changes are found constantly it indicates that they are due to a common pathological cause. Local softening and necrosis, which often accompany the above-mentioned processes, are of sufficient importance to account for the changes in development, which is otherwise normal, to produce spina bifida and the like. These changes, which often take place in the embryo before the blood-vessels are formed, may be likened to those accompanying inflammation in the adult. However, there is a multiplication of cells as well as a cell necrosis, and Panum thinks himself justified in calling the process parenchymatous inflammation of the embryo.

The tissue changes found by Panum in experimental chick monsters were subsequently seen and recognized by Giaccmini, His, and myself in the human embryo, and are well described by Giaccmini in his general article. By means of serial sections of pathological embryos it is easily seen that the sharp normal lines of demarcation of the structures are largely lost in young embryos; and in older embryos the elements of different organs become more or less mixed, which often gives them the appearance of lymph-glands. However, certain tissues like the ectodermal are more resistant than others. The changes in older embryos were described with great accuracy by His. He stated that the bloodvessels of pathological embryos enlarge and become gorged with blood, and that many of the cells wander into the surrounding tissues, thus converting the whole embryo into an even structure, as described by Giaccmini.

It seems to me, in view of what has been said above, as well as by the results of Born upon grafted embryos, and of Hertwig, Morgan, and others upon numerous experimental monsters, that we are dealing with a condition in which there is more or less correlation of growth, which may represent a fundamental type of inflammation. When, however, the embryonic tissues become mixed, which is generally due to malnutrition followed by some cytolysis, we have a new condition quite unlike any pathological change found in the adult. The repair of a simple wound in the embryo is always associated with further development of the surrounding parts, and in case the process ends in a perfect result normal development still remains, with or without regeneration ; but If there is a lack of correlation, pathological conditions arise, already recognized by Morgagni, and well described by Panum, Giaccmini, and His. This pathological condition I shall term dissociation. The growth of dissociated tissues may be checked by excesssive cytolysis or they may be destroyed entirely by histolysis.

There are several young embryos in my collection in which dissociation is just begimiing. One of them, 2 mm. long, which is practically normal in form, is from au ovum which was curetted from the uterus and included part of the decidua (Fig. 185). The decidua is infiltrated with leucocytes and the eoelom has in it an excess of magma reticule; otherwise the chorion appears normal. The front end of the amnion is torn and well packed in with magma, showing that it too is not of mechanical origin. In general, this specimen shows that in young pathological ova the embryo is extremely susceptible and about the first to suffer. In this specimen the mesodermal tissue of the embryo and the ventricles of the fore-brain are filled with round cells containing fragmented nuclei. Most of the blood-corpuscles are still within the blood-vessels, and those that are free in the tissues are well defined and perfectly normal in appearance. However, it may be noted that the cells of the mesenchyme diminish as the free round cells increase, showing that they are dissociating, as are also those of the brain tube. Another specimen, somewhat more advanced in development, has an atrophic head and a wide open spinal cord below, anencephaly and spina bifida (Fig. 186). In this there are f.r^-Z^r^S'^: ^^,.Tri.^:LtTJtf slight signs of its pathological the ovum « BO ram. The abortion took place 18 nature in the chorion, and there weeki after the last menstrual penod. . . n

IS an excessive amount of magma in the coelom. So far there is no dissociation of the tissues of the embryo; there is only an arrest of development of the central nervous system. As the pathological process continues in later embryos of the fourth week, the amnion is often destroyed and tlie embryo rapidly degenerates, usually leaving the umbilical vesicle, which is quite resistant. Subsequently this is also destroyed, leaving only the chorion, without amnion or embryo, which may continue to grow into an irregular mole. The embryo gradually becomes more and more resistant during the fifth week, the brain and heart showing somewhat greater resistance than tie other organs. -Between the fifth and sixth weeks, when the peripheral nervous system appears, the delineation of the organs becomes sharper. Here we also often find dissociation of one or more of the tissues or organs, a gorged vascular system, and frequent hydrocephalus, all probably due to an arrest of the heart action. Such embryos rapidly undergo secondary changes and within a month most of them abort, or if the chorion remains it may form the nucleus of a mole.

During the sixth week, owing, no doubt, to the unequal differentiation of the tissues, some of them become more resistant than others. The more central tissues stand the action better and the more peripheral tissues are more susceptible. Thus the spinal cord and medulla do not dissociate and atrophy so easily as do the head, face, brain, and extremities. The vascular system also suffers very much, probably on account of the effect of the impaired nutrition of the chorion upon the heart. As a result of the weakened heart the cavities of the brain and body become dropsical, and the tissues of the extreme ends of the embryo dissociate and develop poorly. The precartilage^ and cartilages suffer least of all.

In the beginning of the seventh week the cartilages of the extremities are outlined, and at the end of this week ossification centres make their appearance. Coincidently the peripheral nerves ramify through the body and the muscle anlagen appear. On account of the high degree of differentiation of the structures of the embryo, impairment of its nutrition produces very imequal effects upon its organs and tissues. In the earliest stages the umbilical vesicle is the most resistant, liien the nervous system, and now it is the skeletal tissues. Before the development of the heart, the bloodvessels were verjresistant; now that they are dependent upon the heart they are least resistant, and structures which are dependent upon the circulation for their nutrition suffer in a secondary way. The changes in embryos of the seventh week can be followed easier than those in earlier embryos, for they are less rapid and the differentiation of the structures aids the observer very' much. Now the extreme ends of the embryo are profoundly changed (Fig. 187), due probably to affections of the heart of the embryo; there is much cytolysis and dissociation of the nervous system; and the face, head, and extremities are often atrophic. Towards the eighth week there is a great Fia.iM.— Reomatnictioaoftha diminution of the number of pathological 2* mip. long. Bhowing .pin. bifid*, ova lu mv collection, as was also th6 case X'^ft?i^!'°^'^"*'"~" in that of His. It follows that most monsters are fortned before the eighth week; those with radical changes in them are aborted, while those that are slightly affected continue to develop until the end of pregnancy. However, many of those that are aborted show considerable growth of a variety of structures, such as the epidermis, which proves conclusively that we are not dealing with post-mortem changes in the embryo. The longer such a specimen remains in the uterus the more radical are the secondary changes in the embryo and the more pronounced are the primary changes in the chorion. In order that a monster shall continue throughout pregnancy the changes in the embryo must not be extreme enough to eliminate the heart, and the chorion must be normal enough to permit the formation of a healthy placenta, which begins to differentiate at the time (end of the second month) monsters cease to form.

In the following table I have arranged the data regarding the percentage of the varieties of monsters found in pathological ova, and at birth. In general they agree very well. However, the percentage of spina bifida is greater in the embryo than at birth, indicating that the mortality is greatest in this variety of monster. If the larger number of cases of dropsy of the head were reduced or omitted, the proportion of monsters in pathological ova and those at birth would agree very well. No doubt water on the brain is an affection primarily of later fetal life, but this question remains to be investigated.

Keibel Mall Pathology-table3.jpg

The specific action of salt solution upon amphibian eggs, producing a large percentage of spina bifida monsters, has been mentioned above. The work of Torneau and Martin, and more recently that of Fischel, has shown that spina bifida in man is not only to be viewed as an arrest of development of the medullary plate, leaving the neural tube open, but that there is also a secondary destruction of the meiubrana reuniens behind, at least in all cases of spina bifida occulta (Figs. 188-190). Deformities of the head, such as anencephaly (Figs. 191-193) and, what may often follow it, cyclopia {Figs. 194 and 195), are now easily understood, since we have the splendid experiments of Stockard and of Lewis upon this question in Fundulus. That the great varieties of dropsy, as pictured by Kollmann and as are frequently seen in embryos and fetuses, are due to an impairment of the action of the heart is now definitely proved by the enucleation experiments of Knower. It is no longer necessary for us to seek for mechanical obstructions which may compress the umbilical cord, such as amniotic bands, for it is now clear that the impairment of nutrition which naturally follows faulty implantation, or the various poisons which may be in a diseased uterus, can do the whole mischief. That monsters group themselves, both in nature and when made experimentally, rather shows that certain tissues are influenced at crucial periods in their development, and not that given substances have specific influences upon the embryo as a whole.


Keibel Mall 191.jpg

Fig. 191. — Embryo 16 mm. loof,

Keibel Mall 192.jpg

Fig. 192.


Keibel Mall 193.jpg

Fig. 193. — Section of Ihs chorionia villi of the spedoiea al: relieulum batween


Aulfeld: Geburtshilfe, 1903. Die Missbildungen des Menschen, Leipzig, 1880-1882.

Bardeen : Jour, of Experimental ZooL, 1907.

Ballantyne: Antenatal Pathology, 2 volumes, Edinburgh, 1904.

Bischoff: Wagner's Handworterbueh, 1842.

Born: Roux's Archiv, vol. iv, 1897.

Dareste: Recherches sur la production de monstruosites, Paris, 1891.

Driesch : Zeit. f . wiss. Zool., vol. Iv, 1892.

Eycleshymer: Amer. Jour. Anat., vol. vii, 1907.

Fischel: Ziegler's Beitrage, vol. xli, 1907.

Forster: Die Missbildungen des Menschen, Jena, 1865.

GiaccMiKi, Merkel, and Bonnet, Ergebnisse, vol. iv, 1894.

Gerlacu: Doppelmissbildungen, 1882.

Granville: Graphic Illustrations of Abortion, London, 1834.

Harrison: Amer. Jour. Anat., vol. iii, 1904.

Hertwig, 0.: Arch. f. mik. Anat., vol. xxxix, 1892; vol. xliv, 1895. G^genbaur Festschrift, vol. ii, 1896. Handbuch d. Vergl. u. Experiment. Entwicklg. d. Wirbeltiere, vol. L

Hegar : Monatseh. f iir Geburtskunde, vol. Ixi, 1863.

Hirst and Piersol: Human Monsters, Philadelphia.

His: Anatomie menschl. Embryonen, vol. ii, 1882. Virchow Festschrift, vol. i, 1899. EIelly: Operative Gynaecology, vol. ii, Philadelphia.

Knower: Anatomical Record, vol. i, 1907. Koch: Beitrage zur Lehre von spina bifida, Kassel, 1881.

Kollmann: Archiv fiir Anat. u. Entwicklgesch., Supplement-Band, 1899. Leopold: Arbeiten aus der dresdener Frauenklinik, vol. iv. Leuckart: De Monstris, Gottingem, 1845.

Levy : Roux's Archiv, vol. xx, 1906.

Lewis: The Experimental Production of Cyclopia in the Fish Embryo, Anatom. Record, vol. iii, 1908.

Loeb: Biological Lectures at Woods Holl, 1893; PflUger's Archiv, vol. liv, 1893; ibid., vol. Iv, 1894 ; Roux's Archiv, vol. i, 1895 ; and Studies in General Physiology, Chapter X, Chicago, 1905.

Mall: Welch Festschrift, Johns Hopkins Hospital Reports, vol. ix, 1900. Vaughan Festschrift, Contributions to Medical Research, Ann Arbor, 1903. Johns Hopkins Hospital Bulletin, 1903. Anatomical Record, January 1, 1907. A Study of the Causes Underlying the Origin of Human Monsters, Jour. Morph., vol. xix, 1908 (contains a full description of all the specimens used in this chapter).

Marchand: Missbildungen, Eulenburg's Real-Encyclopaedia, third edition, 1897, vol. XV.

Meckel, J. F. : Handbuch d. pathol. Anatomica Leipzig, 1812.

Morgan : Ten Studies in Roux's Archiv, vols, xv-xix, 1902-1905.

Morgan and Tsuda: Quart. Joum. Micr. Sci., N. S., vol. xxxv, 1894.

Muller: MeckeFs Archiv, 1828.

Panum: Entstehung der Missbildungen, 1860.

Piersol: Teratology Ref. Hndbk. Med. Sci., new edition, vol. vii.

Von Recklinghausen: Virch. Arch., vol. cv, 1886.

Richter: Anat. Anz., vol. iii, 1888.

Schaper: Jour. Bost. Soc. Med. Sci., 1898; and Roux's Archiv, vol. \'i.

ScHULTZE, 0. : Verhandl. d. anat. Gesellsch., 1894 ; and Roux's Archiv, vol. i, 1895. Vol. T.— 16

ScHWALBE, E. : Die Morphologie d. Missbildungen des Menschen und der Thiere, Jena, part i, 1906, part ii, 1907.

Spemann : Stizungsber. d. phys.-med. Gesellsch., Wurzburg, 1900. Ronx's Archiv, vol. xv, 1903; and Zool. Jahrbiicher, vol. vii, Supplement, 1904.

Stockakd : Roux's Archiv, vol. xxiii, 1907 ; also Jour. Elx. Zool., vol. vi, 1909. Tarutfi: Storia delli Teratologia, 8 volumes, Bologna, 1881-1895.

ToRNEAU and Martin: Journal d'Anat. et Physiol., vol. xvii, 1881.

Tornier: Roux's Archiv, vol. xx, 1905. Valentin: Handworterbuch d. Physiologic, vol. i, 1842.

Vejdovsky: Entwicklsg. Untersuchungen, Prag, 1890. Voigt: Anatom. Hefte, vol. xxx, 1906.

Wetzel: Arch. f. mik. Anat., vol. xlvi, 1895.

Williams: Obstetrics, New York, 1903.

Wilson : Jour, of Morph., 1893.

Von Winckel: Ueber die Missbildung von ektopisch. entwichten Fruchten, Wiesbaden, 1902. Ueber die menschl. Missbildungen, Saimnl. klin. Vortrage, Leipzig, 1904.

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