Book - Contributions to Embryology Carnegie Institution No.56-7

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Mall FP. and Meyer AW. Studies on abortuses: a survey of pathologic ova in the Carnegie Embryological Collection. (1921) Contrib. Embryol., Carnegie Inst. Wash. Publ. 275, 12: 1-364.

In this historic 1921 pathology paper, figures and plates of abnormal embryos are not suitable for young students.

1921 Carnegie Collection - Abnormal: Preface | 1 Collection origin | 2 Care and utilization | 3 Classification | 4 Pathologic analysis | 5 Size | 6 Sex incidence | 7 Localized anomalies | 8 Hydatiform uterine | 9 Hydatiform tubal | Chapter 10 Alleged superfetation | 11 Ovarian Pregnancy | 12 Lysis and resorption | 13 Postmortem intrauterine | 14 Hofbauer cells | 15 Villi | 16 Villous nodules | 17 Syphilitic changes | 18 Aspects | Bibliography | Figures | Contribution No.56 | Contributions Series | Embryology History

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Chapter 7. The Occurrence of Localized Anomalies in Human Embryos and Fetuses

In a paper on the causes underlying the origin of human monsters (Mall, 1908), I made the assertion that localized anomalies were more common in embryos obtained from abortions than in full-term fetuses, without, however, adducing conclusive evidence in support of this theory.


In a footnote on page 27 of that publication I gave a list of embryos with thenchief defects, comparing them with the percentage of frequency of monsters born at term. Objection might be raised to such a statement on the ground that there is not a complete correspondence between anomalies in the embryo and those found in the fetus at the end of pregnancy. For instance, spina bifida in young embryos is always complete, while at full term the open canal is covered over with skin. Cyclopia and exomphaly are the same in the embryo as at birth, but the deformities of the head and neck of the embryo are of such a nature that it can not survive long enough to admit of comparison with similar malformations found at term. With these difficulties clearly before me, I have made an effort to sharply define the anomalies in embryos, so that a satisfactory comparison might be made with those found in monsters at the end of pregnancy, as described in the literature.


Cyclopia is, perhaps, the type of anomaly which is now best understood, due largely to the excellent experimental work of Stockard, and also partly to the fact that the cyclopean state can exist quite independently of other marked deformities. I have already discussed the question of cyclopia in a separate publication (Mall, 1917 a ), and it is not therefore necessary for me to dilate further upon it at present. Hare-lip is also sharply defined in the embryo and is as readily distinguished as exomphaly. Other anomalies, however, are more difficult to recognize in the embryo as sharply defined malformations.


The pathological specimens of the first 400 accessions to our collection were reported in my paper on the origin of human monsters mentioned above. Since the embryological collection has been taken over by the Carnegie Institution of Washington it has grown at a very rapid rate, about 400 specimens being added to it each year. At present, however, only the first 1,000 will be considered, the remainder not having been sufficiently tabulated to be of statistical value. The specimens can clearly be divided into two groups according to their origin, i. e., uterine and ectopic. In both of these the embryos which are normal in form are catalogued according to then- sitting height, which we call crown-rump (CR). The chief difficulty, however, is to determine what constitutes a normal embryo, and here we must rely largely upon our experience in human and comparative embryology. A sharply defined, well-formed, white embryo, with blood-vessels shining through its transparent tissues, is considered normal. If it is partly stunted and opaque or disintegrating it is considered pathological. A further study of the so-called normal embryos, however, shows that in many of them the membranes are decidedly pathological. For instance, the villi may be deformed, diseased, atrophic or hypertrophic, or the contents of the amnion and the exocoelom may be unusual. Nevertheless, in all of these cases we still classify the embryos as normal, although fully cognizant of the fact that the surrounding membranes are pathological; otherwise it would be difficult to account for the great number of spontaneous abortions. The theory is that the embryo was developed under pathological conditions, but that the chorion was not sufficiently affected to cause any apparent change in the embryo. If an embryo included in this group is apparently normal in all respects save one, we still consider it normal with a localized anomaly. In fact, we are gradually forced into this position, as an embryo, at first regarded as normal, may later prove to have a localized anomaly, such as spina bifida or cyclopia. As far as we can determine, such an embryo would have been able to survive longer had not something happened to its membranes, thus causing its expulsion. I am inclined to believe that pregnancies of this sort, if carried to term, would produce the ordinary monsters described by teratologists.


The second group of specimens, which are termed pathological, are in a way more interesting, and their study justifies our method of classifying localized anomalies with normal embryos. We have in this group a variety of changes ranging from those found in fetus compressus down to complete disintegration of the ovum, leaving only a few villi.


Having made numerous efforts to classify these specimens, I have finally resolved them into seven groups, which have been considered in a previous chapter. It can be readily seen that this classification into sub-groups is arranged somewhat in the order of the age of the ovum when it began to degenerate. Generally the changes are so pronounced that the embryo could not have lived through the duration of pregnancy, and this accounts for the abortion.


We naturally do not find localized anomalies in specimens from the first four groups, while in the remaining three groups we encounter only such as are very pronounced and stand out clearly in spite of other changes. Thus, for instance, with fetus compressus we frequently recognize club-foot; in stunted forms, hare-lip and spina bifida; and in cylindrical forms, spina bifida. If cyclopia is encountered in any of these forms, it is looked upon as a localized anomaly in a pathological embryo. On the other hand, a single anomaly in an embryo called normal can easily be recognized, and it is from this group that we should expect the development of monsters had the pregnancy progressed to term.


A few illustrations of localized anomalies are given here in order to show that they are identical with those found in infants at birth.

Figures 83 and 84 represent, respectively, a cyclopean and a double monster, the embryos being otherwise normal.

Figures 85 and 86 show hare-lip in an embryo and a fetus.

Figures 87, 88, and 89 have pronounced localized anomalies and need no further explanation.

Finally, figures 90 to 93 show anomalies of the hands. The first and last are of the hereditary variety, while figures 91 and 92 are acquired anomalies that is, they were subsequently formed in an embryo whose development began normally.

It is proper to remark here that these illustrations are mostly from specimens from the second 1,000 of our collection. This is because we have recently made many more photographs, and, furthermore, many of the specimens in the first thousand have already been figured in my paper on monsters.


In order to render possible a comparison between localized anomalies found in pathological, and those found in normal embryos, six tables have been constructed. Table 7 gives the classified distribution of the first 1,000 embryos in the Carnegie Collection. The primary division comprises two classes pathological and normal. The pathological specimens in turn are arranged in the seven groups just described. The normal are arranged in groups to correspond as nearly as possible to the ages of the embryos in lunar months. In order to define clearly which embryos belong in a given month, I have inserted their probable lengths for each month in table 12. Thus, for instance, the second month includes all specimens from 2.6 mm. to 25 mm. in length, etc. (Data upon the estimated ages of embryos may be found in my chapter on that subject in the Manual of Human Embryology, vol. 1.)

Table 7. Showing the distribution of first 1,000 accessions

It will be noted in these tables that the specimens are arranged in centuries; that is, each line in the table includes exactly 100 specimens. The first century includes specimens Nos. 1 to 98, the second, Nos. 99 to 205, and so on. This adjustment was necessary for the reason that frequently a single number is given to 2 or more specimens. Sometimes the first is called a and the second b; or the first may be given the number and the second the letter a, etc. The second century, passing from Nos. 99 to 205, includes more than 100 numbers, because specimens which are given a number are frequently found upon further examination to contain no remnants of an ovum, and for this reason they have to be discarded. In our catalogue they are later marked as "No pregnancy." Finally, the tenth century ends with embryo No. 900#. The individual entries are percentage records. Thus in the fifth century there are 41 normal specimens of the second month; that is, of this hundred specimens 41 per cent are normal embryos of the second month, whereas the total for the full 1,000 has brought down this percentage to 24.5.


In determining normality, the criterion used was the shape of the embryo, judging this as best we could by our own knowledge of human and comparative embryology, as well as by the experience of other students of human embryology. We have also used freely the atlases of His, Hochstetter, and Keibel and Else in making our decisions on this point. However, many of these specimens are inclosed in membranes which have undergone very marked changes. Thus, an embryo normal in form may be found to be surrounded by an excessive amount of magma and the chorion may have undergone very pronounced changes; but for purposes of classification we have found it necessary to arrange them all according to the shape of the embryo. A fairly large number of our specimens were obtained from hysterectomies. We believe with Hochstetter that we shall ultimately have to determine what constitutes a normally formed human embryo from specimens obtained in this way; but among about 25 hysterectomy specimens, we nevertheless found 3 which were markedly pathological and undergoing abortion.

Table 8. Distribution of uterine specimens

Table 9. Distribution of ectopic specimens

Table 8 includes all uterine and table 9 all ectopic specimens. In comparing these three tables it will at once be noted that among the entire 1,000 nearly 40 per cent are pathological embryos and ova. Of this number 31 per cent were obtained from the uterus, while slightly more than 8 per cent were ectopic. The comparative frequency of pathological and normal embryos can be ascertained, however, by comparing them within a given century, or for the whole 1,000 together. In the uterine specimens about one-third of the ova and embryos are pathological, as compared to two-thirds in the ectopic. In other words, pathological specimens are twice as frequent in ectopic as in uterine pregnancy.


Table 10 includes all the specimens in which there are pronounced localized anomalies. The character of the anomaly for the individual specimens recorded is given in tables 11 and 12. From these tables it would appear that there are about as many anomalies among the normal as among the pathological specimens, but when these figures are compared with the total number of specimens, both normal and pathological, it becomes evident that localized anomalies occur about twice as frequently in the pathological as in the normal embryo. Thus, 38 out of 396 pathological specimens, or about 10 per cent, exhibit localized anomalies, as against 6 per cent in 604 normal specimens. The 38 pathological specimens with localized anomalies listed in table 10 were aborted in the early part of pregnancy, and only one of them (No. 649) grew to a sitting height of 90 mm., that is, to about the middle of the fourth month.

Table 10. Distribution of specimens with localized anomalies (to be compared with table 7)

The number of normal embryos with localized anomalies tends to decrease before the fifth month, there being but 1 in the sixth, 1 in the eighth, and 4 in the tenth month, the end of pregnancy. In other words, all pathological specimens, either with or without localized anomalies, are aborted in the first half of pregnancy, as are also nearly all so-called normal embryos with slight malformations, very few of them reaching full term.


We have made an especial effort to collect specimens of full-term monsters as well as abortion material from all months of pregnancy. Only the first 100 specimens of the collection show an unusually large percentage of normal embryos. Although at first an effort was made to collect only good, normal specimens, the last 900, including all sorts of material, carry about the same percentage of normal specimens throughout. Among the first 1,000 specimens of our collection there are not many fetuses from the second half of pregnancy, but we are now endeavoring to collect material covering all months. One monster at term, a sympus belonging in about the third 100, was not recorded in our catalogue, and should be added to the four full-term specimens given in table 10. This means that among 1,001 specimens there were 5 full-term monsters, while among 1,000 specimens there were 71 with localized anomalies, most of them being aborted early in pregnancy.

Table 11. Localized anomalies in pathological embryos

According to the table on the frequency of abortions, given in my monograph on monsters (Mall, 1908), there are 20 abortions to every 80 full-term births; therefore, the 1,000 abortions under consideration were probably derived from 5,000 pregnancies.


As we have calculated that there should be approximately 30 full-term monsters in 5,000 pregnancies, and as 5 of these were observed in our 1,000 specimens, it is apparent that the remaining 25 should be encountered in 4,000 additional full-term births. When these figures are considered in connection with the fact that 75 localized anomalies occurred in 1,000 abortions (7.5 per cent) it becomes apparent that in any similar numbers of abortions localized anomalies should occur twelve times as frequently as monsters at term. A similar result is obtained if the number of localized anomalies of the tenth month, as given in table 10, is compared with all of the localized anomalies of previous months, as given in the same table.


Our studies seem to justify the conclusion that pathological embryos, as well as those which are normal in form, are very frequently associated with localized anomalies and that abortion usually follows as a result of serious lesions in the chorion, as well as in its environment. Should the alterations in the embryo and in the chorion be very slight and the condition of the uterine mucous membrane, which may be expressed by the term inflammation, be overcome, the pregnancy in all probability would go to term and end in the birth of a monster or an infant presenting a well-recognized malformation.

Table 12. Localized anomalies in normal embryos

I have already pointed out the difference in frequency of malformations and destructive changes, as observed in the ovum, in tubal and in uterine pregnancies. Since the publication of my monograph on monsters I have reconsidered the question of tubal pregnancy and the specimens mentioned in the present paper are recorded in detail in a volume on tubal pregnancy (Mall, 1915).


It seems to me that the studies based upon our collection, as well as recent investigations in experimental embryology, set at rest for all time the question of the causation of monsters. It has been my aim to demonstrate that the embryos found in pathological human ova and those obtained experimentally in animals are not merely Analogous or similar, but identical. A double-monster fish or a cyclopean fish is identical with the same condition in human beings. Monsters are produced by external influences acting upon the ovum; as, for instance, varnishing the shell of a hen's egg or changing its temperature, traumatic and mechanical agencies, magnetic and electrical influences, as well as alteration of the character of the surrounding gases, or the injection of poisons into the white of an egg. In aquatic animals monsters may be produced by similar methods. Whether in the end all malformations are brought about by some simple mechanism, such, for instance, as alteration in the amount of oxygen or some other gas, remains to be demonstrated. The specimens under consideration show such marked primary changes in the villi of the chorion and in the surrounding decidua that the conditions in the human may be considered equivalent or practically identical with those created artificially in the production of abnormal development in animals.


It would be quite simple to conclude that the poisons produced by an inflamed uterus should be viewed as the sole cause, but when it is recalled that pathological ova occur far more commonly in tubal than in uterine pregnancy, such a theory becomes untenable. Moreover, monsters are frequently observed in swine and other animals without any indication of an inflammatory environment. For this reason I have sought the primary factor in a condition buried in the non-committal term, faulty implantation. It would seem to be apparent that lesions occurring in the chorion as the result of faulty implantation can and must be reflected in the embryo. For example, before circulation has developed in a human embryo, pabulum passes from the chorion to the embryo directly through the exoccelom, and probably on this account we always encounter, as a first indication of pathological development, a change in the magma. In older specimens, before any other changes are noticeable in the ovum, the magma becomes markedly increased and a variety of changes are found between the villi. I shall not dwell further upon magma, as I have already dealt with the subject in detail (Mall, 1916).


It is perfectly clear that, in general, monsters are not due to germinal or hereditary causes, but are produced from normal embryos by influences which are to be sought in their environment. Consequently, if these influences are carried to the embryo by means of fluids which reach it either before or after the circulation has become established, it would not be very far amiss to attribute these conditions to alterations in the nutrition of the embryo. Probably it would be more nearly correct to state that change in environment has affected the metabolism of the egg. Kellicott (1916), who has discussed this question, seems to be disinclined to accept such an explanation, but I do not see that he has added materially to it by substituting the word disorganization for nutrition, as one might as easily say that the altered nutrition causes the disorganization.


In my paper on monsters I stated that on account of faulty implantation of the chorion the nutrition of the embryo is affected, so that if the ovum is very young the entire embryo is soon destroyed, leaving only the umbilical vesicle within the chorion; this also soon disintegrates, and the chorionic membrane in turn collapses, breaks down, and finally disappears entirely. In older specimens, on the other hand, the process of destruction takes place more slowly, and thus we many account for a succession of phenomena which correspond to the seven groups of pathological ova referred to above.


Kellicott, in his discussion of monsters, dropped the subject by stating that the embryo is a monster simply because it is disorganized. In my original study I really went, I believe, a step farther than Kellicott, for I attempted to analyze the process of disorganization more thoroughly and demonstrated that in the beginning it is accompanied by cytolysis, but as it progresses more rapidly it results in histolysis, and that these two processes do not act with equal severity on all parts of the embryo. When we consider the ovum as whole, it is the embryo itself which is first destroyed, while within the embryo the central nervous system or the heart is the structure first affected. Morphologically, these changes are accompanied by a destruction of certain cells and tissues, leaving other portions which continue to grow in an irregular manner. For this reason I speak of the tissues which are first affected as being more susceptible than the others. The entire process of disorganization, resulting in an irregular product, I have termed dissociation. In a general way this explanation is accepted by Werber (1915, 1916), but he employs the term blastolysis instead.


At the time I prepared my paper on monsters, Harrison was just beginning his interesting experiments in tissue culture in our laboratory. Since then this method of study has given us clearer insight into the independent growth of tissues. I was fully convinced from the study of pathological embryos that tissues continue to grow in an irregular manner, thus arresting normal development; but since we are more familiar with the growth of tissues, as revealed by Harrison's method, we can understand a little better the process of dissociation. In fact, we have in our collection two striking examples of tissue culture in human embryos. In one the cells had formed an irregular mass which was growing actively, but the contour of the organs had been entirely lost. In the other, from a tubal pregnancy, for some unknown reason the ovum had been completely broken into two parts, which in turn had cracked the embryo, and from each piece there had been a vigorous independent tissue growth, or, as we may now say, a tissue culture. Accordingly, when an embryo is profoundly affected by changed environment the development of one part of the body may be arrested, while the remaining portion may continue to grow and develop in an irregular manner. In very young embryos, tissues or even entire organs become disintegrated, as can be easily recognized by the cytolysis and histolysis present, and the resultant disorganized tissue can not continue to produce the normal form of an embryo. If this process is sharply localized, for instance, in a portion of the spinal cord or in the brain, spina bifida or anencephaly results. To produce a striking result, as in cyclopia, a small portion of the brain must be affected at the critical time, and I think the work of Stockard has shown clearly that this is before the eye primordia can be seen. Consequently, in order to produce a human monster which is to live until the end of gestation, the effect of the altered environment must be reflected from the chorion to the embryo, so that the tissue to be affected is struck at the critical time in its development. It is inconceivable that cyclopia should begin in an embryo after the eyes are once started in normal development. Moreover, the same is true regarding hare-lip, for after the upper jaw has once been well formed, the abnormality can not develop. We may extend this statement to include club-foot, spina bifida occulta, and other types of malformation. In fact, in discussing the origin of merosomatous monsters, hardly more has been stated by most authors than that there has been an arrest of development, but I have attempted to point out that the primary cause is in the environment of the egg and that the arrested development is associated with destruction of tissue.

Description of Plate

Plate 7

Mall Meyer1921 plate07.jpg

Fig. 83. Normal embryo with cyclopia ; in front of the eye is seen the Cyclopean snout. No. 559. X3.75.

Fig. 84. Normal double monster. No. 249. X0.75.

Fig. 85. Specimen with hare-lip and exencephaly. No. 364. X2.25.

Fig. 86. Specimen with hare-lip. No. 982. XI. 5.

Fig. 87. Stunted fetus with large hernia in umbilical cord. No. 1330. X0.9.

Fig. 88. Normal embryo with exencephaly and spina bifida (the latter opposite the arrow). No. 1315. XI. 5.

Fig. 89. Normal fetus with hernia of mid-brain. No. 1690. X6.75.

Fig. 90. Anomaly of left hand of No. 306a. Only the thumb and little finger are normal.

Fig. 91. Left hand, which is club-shaped, from No. 230, a fetus compressus 57 mm. CR. X0.75.

Fig. 92. Deformed wrist with atrophic radius in a normal embryo. No. 789, 50 mm. CR. X3.

Fig. 93. Right hand with six fingers from macerated specimen. No. 1749. There were six digits on each of the four extremities. X3.

Fig. 94. Hydatiform villi. (After Gierse.) See Chapter VIII.

Fig. 95. Hydatiform villi showing vacuolation. (After Gierse.) See Chapter VIII.

Plate 7: Fig. 83 | Fig. 84 | Fig. 85 | Fig. 86 | Fig. 87 | Fig. 88 | Fig. 89 | Fig. 90 | Fig. 91 | Fig. 92 | Chapter 7 Localized anomalies


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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Mall FP. and Meyer AW. Studies on abortuses: a survey of pathologic ova in the Carnegie Embryological Collection. (1921) Contrib. Embryol., Carnegie Inst. Wash. Publ. 275, 12: 1-364.

In this historic 1921 pathology paper, figures and plates of abnormal embryos are not suitable for young students.

1921 Carnegie Collection - Abnormal: Preface | 1 Collection origin | 2 Care and utilization | 3 Classification | 4 Pathologic analysis | 5 Size | 6 Sex incidence | 7 Localized anomalies | 8 Hydatiform uterine | 9 Hydatiform tubal | Chapter 10 Alleged superfetation | 11 Ovarian Pregnancy | 12 Lysis and resorption | 13 Postmortem intrauterine | 14 Hofbauer cells | 15 Villi | 16 Villous nodules | 17 Syphilitic changes | 18 Aspects | Bibliography | Figures | Contribution No.56 | Contributions Series | Embryology History

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)