Paper - A study of the causes underlying the origin of human monsters 18
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Mall FP. A study of the causes underlying the origin of human monsters. (1908) J Morphol. 19: 3-368.
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A Study Of The Causes Underlying The Origin Of Human Monsters
Embryos of the Sixth Week
In the beginning of the sixth week of development the cartilages of the extremities are outlined, and at the end of the week some of the ossiﬁcation centers are present. Coincidentally the peripheral nerves ramify through the body and the muscle anlages appear. Thus we have before us a highly differentiated organism, and from now on anything which affects its nutrition does not produce a like inﬂuence in all of its tissues and organs. The reader has noticed, no doubt, that the present study is gradually Ieacling in this direction. First the umbilical vesicle is most resistant, then the nervous system and now it is the skeleton. At first the blood-vessels possess the greatest power of growth before they were dependent upon the heart, but later when they are, they appear to suffer most, and the other structures are only affected in a secondary way, for they in turn receive their nutrition from the blood.
The changes in embryos of the sixth week can be followed with greater case than those in earlier embryos, for they are less rapid and there are a larger number of known structures present to tell the story. In studying the pathological embryos, I naturally compare these changes with the normal in embryos of about the same age, and as a standard Nos. 109 and 144 are constantly employed (Plate IV, Fig. 10).
TABLE XII. Nonmu. Eumzvos or THE SIXTH WEEK. I S cimen. Emb o. Choi-ion. E 3 De 17 E < 2 mm. mm. days His.(x9) 12.8 40x32 No. 35 . . . . . . . . . . 13 37
Nc_).175 . . . . . . . .. 13 3ox25x25 32
His (M2) . . . . . . .. I3 64
His (Bra) . . . . . . .. 13.6 35 x 28 63
No. 144 . . . . . . . .. 14 40 x 30 x 30 60
No. 214 . . . . . . . .. I4. 27x25x15
No. 360 . . . . . . . .. I4 55
No. 167 . . . . . . . .. 14.5 3ox3ox3o 65
No. 168 . . . . . . . . . 15 94
His (Drr) . . . . . .. I5 45 x 40
His (S2) . . . . . . . . . I5 35 x 28
No. 256 . . . . . . . .. :6 6o
No. 17 . . . . . . . . .. 16 45x35x25 His gLhs) 17 51 No. 106 . . . . . . . . .. I7 54 No.216 . . . . . . . . .. 17 35x35x25
The ﬁrst pathological specimen which I shall consider is No. 311, an unusually good one, for it is well preserved and there is every indication that the changes in it were produced gradually. Unfortunately, the menstrual age is not known, but L am of the opinion that it must be at least ﬁfty days, that is, about two weeks more than normal embryos of the same size and degree of.development. The chorion is covered with villi of unequal size, which show all degrees of activity, some being hypertrophic and others atrophic, ﬁbrous and more or less invaded by leucocytes. The surrounding inﬂammatory process has gradually destroyed the villi. The condition of the vessels within the villi also indicates that the process of destruction has been gradual; the large villi contain fairly well developed capillaries, and the small ones are devoid of them altogether. The umbilical cord is enlarged in its center and very -small at its attachment to the chorion. In general, it is ﬁbrous and its blood-vessels are contracted and empty. The enlargement in the cord is due to the mucoid masses
TABLE XIII. ARRESTED DEVELOPMENT or rm: Emmvo. (Sixth Week.) No. Iégglgfgoff D=n5ggj1ig;§ 0‘ Mergggal Changes in the Chorion. mm. mm. days. 311 12} 36x3ox3o Fibrous. 69 13 7o x 4o x 20 Atrophic and ﬁbrous
174 I3 35 x 25 x 25 56 Atrop_h1c'. Invaded by syncytium.
182 I 3 H 1_
2 1 x x - a me.
34?; 1: 55 505%?) 35 73 Ngrmal. Mucus and pus between villi.
37 5 13 Fibrous.
276 13; 7o x 35 x 35 8o Fibrous.
232 14 45x25x25 F1bI'0}1S (?).
262 I4 80 x 15 x 15 Villi invaded by leucocytes.
270 14 4o x 3o x 2o Fibrous and atrophic.
365 I4 , . .
341 14 70 X 60 x 50 Fibrous. Some villi oedematous. (Twins in a single chorion.)
81 15 65 x 55 x 35 84 Atrophic, inﬁltrated with leucocytes.
132 15 42 x 30 89 Atrophic.
r42 15 50 x 40 X 30 129 Fibrous. Invaded by syncy— tium.
200 15 3 x 25 x 15 Fibrous.
212 15 ery large 189 (?) _
364 16 90 x 5o x 40 99 Fibrous and atrophic.
137 I6 60 x 50 x 30 86 Fibrous. _
207 :6 7o x 45 x 45 Chorion hyalme(?). Syncytium irregular. Decidua inﬁltrated with leucoytes. (Tvvins in a. single chorion.)
339 :6 50 x 3o x 3o Hyalme. _
344 :6 45 x 45 x 45 Fibrous and atrophic.
203d 15 27 x 27 x 27 Normal(?).
188 17 45 x 40 x 40 66 Very ﬁbrous.
215 17 45 x 40 x 40 12 wks. Fibrous.
357 17 90 x 4o x 4o 13 wks Fibrous. Invaded by syncytium.
within, seen so often in pathological specimens.
Within the embryo the vascular system and heart are much dilated and ﬁlled with blood. The whole condition of affairs indicates that the circulation was interrupted shortly before the abortion took place.
The embryo is imbedded in an irregular mass of granular magma, and from its external form it seems to be nearly normal. However, its neck is kinked too much in front, and sections show that there is an active growth of scar tissue at this point. In general, all the tissues are more or less dissociated, the cartilages and precartilages being most resistant. The walls of the heart and blood-vessels are not sharply deﬁned and many blood cells spread from them into the surrounding tissues. The central canal of the spinal cord is distended and the peripheral nerves are well inﬁltrated with round cells. The dissociation of the fore—brain and mid—brrain is pretty complete, and the walls of the medulla are spreading out into its ventricle. In general, the head is reduced in size,
The most marked secondary changes are seen in the mesenchyme of this specimen. At points there are ﬁbrous thickenings in the skin, which frequently form papillomata, covered more or less with a single layer of epithelium. In front the face and chest have grown together, the point of union naturally closing the mouth, including the tip of the tongue in a mass of round cells.
I picture the whole process as follows: In general, the destruction of villi in the chorion is followed by ﬁbrous atrophy of the umbilical cord and arrest of the heart beat. After the circulation has ceased the organs and tissues gradually dissociate and blood cells enter the tissues. Probably before the changed conditions had reached this extreme state the brain began to dissociate and became solid, and the face atrophied and united with the chest below. The changes in the rest of the embryo were not marked until the circulation ceased altogether. It is clear, however, that the brain dissociates before the rest of the embryo, for we constantly ﬁnd in it more radical changes than in other portions of the embryo.
Practically the same pathological changes described for specimen No. 311 are found in Nos. 375, 69, I74, 182 and 325. No. I74 has horn-like processes and No. 182 has a straw-colored necrotic mass in front of the head. No. 325 shows still more advanced changes, the necrosed liver is disintegrating, this process having begun in 311. From all appearances this embryo has been dead for a long time, which is also indicated by its menstrual history.
Embryos I4 mm. long repeat the story given by those I 3 mm. long. The least amount of change is found in No. 270, which is nearly identical with No. 311. However, the brain is not quite so solid, the dissociation of the tissues of the body is about of the same degree and the frontal process is united to the thorax below. Within the medulla there are papilliform sprouts of nerve tissue which extend into the ventricle, just as in No. 311. No. 346 may be a little older than No. 270, but the changes in it are not quite so advanced, nor has the frontal process united with the thorax below. The head and neck are also straight in Nos. 262 and 232, the changes in the tissues being very advanced. In No. 262 the cerebral hemispheres form a solid mass, which looks like an abscess, the medulla is much distended and its thin anterior wall protrudes through the mouth. Much the same condition is found in the cylindrical head of No. 232. In it the large ﬁfth nerve may be seen running to the surface of the body, and acts as an index to tell how much of the head has become atrophied. The arms and legs are gorged with well stained round cells, indicating that secondary changes have taken place in them.
The marked changes which have taken place in the brain and head have met their end in embryo No. 276. Here we ﬁnd advanced changes in the head, but the body is much like the other specimens. The medulla is greatly distended and ﬁlls entirely the rounded top of the body, the rest of the brain having been expelled through an opening which is still present. Around the edge of it the epidermis is piled upon itself, apparently attempting to heal the wound. The severe changes in the chorion and the long duration of the process have ended by destroying entirely the brain and the top of the head, leaving the body of the embryo capped only with a remnant of a head containing a dissociated medulla.
Most radical changes are found in specimen No. 365. The embryo is within a ﬁbrous chorion. There is spina biﬁda, iniencephaly and anencephaly. The mouth is closed completely by the tongue becoming adherent on all sides. The tissues of the body are necrotic, and most of them are inﬁltrated with round cells, and there is irregular growth of the mesodermal tissues, especially those of the tendons and perichondrium.
The embryos of the second portion of the sixth Week, that is, embryos I5, 16 and 17 mm. long, may be brought together in three groups, according to the degree of change in their tissues.
In the ﬁrst group there are three specimens, Nos. 263d, I 32 and 188. In these the ﬁrst changes are seen after the circulation has been cut off. The tissues and organs are sharply deﬁned, the vascular system is distended with blood, and more or less round cells are found in them. The fore—brain is solid and the medulla and cord are somewhat dissociated. In No. 263d the brain has broken through the palate and a considerable amount of it has escaped into the mouth. However, this embryo is macerated somewhat and is slightly torn in the region of the back, and the brain capsule may have been torn open by mechanical means. In embryo No. I32 the extremities of the right sideof the body are atrophic, while those of the left appear to be normal.
In the second group of specimens (Nos. 344, I37 and 357) the changes in the embryo are more marked. The bloodvessels are gorged, their walls are not sharply deﬁned and the blood cells extend from them into the surrounding tissues. In No. 344 the brain is reduced in size, is solid and occupies but a small portion of the head. The medulla is dissociated and expanded and has been pushed forward, almost reaching to the front part of the head. Below this the jaw is kinked over the chest, with which it has formed a secondary union. Over the regions of the fore-brain and mid-brain there are spots in which all of the surrounding tissue is wanting entirely, thus exposing the brain freely at these points.
The last group includes the embryos in which the changes are extreme, and includes seven specimens, Nos. 81, 142, 200, 212, 215, 339 and 364. In them the tissues are well dissociated and more or less ﬁlled with round cells. The usual changes are seen in the central nervous system, the spinal cord being dilated, while the brain and medulla are solid. In these embryos the dissociation is carried to an extreme degree, the extremities being atrophic, and in some of them the embryos are pretty well disintegrated. In Nos. 8I, 200 and. 212 the face and the top of the head are composed of a thickened mass of necrotic tissue, and the changes in the central nervous system are extreme. The embryo of specimen No. 215 is broken into a number of pieces which barely hold together.
Specimens Nos. I42 and 339 are quite typical ones of this stage, for in them the dissociation of the tissue is pretty complete, and the outlines of the organs are quite obscure. Most of the blood has left the blood-vessels and is in the surrounding tissues. The fore—brain is completely separated from the medulla in No. 339, and in general it is reduced in size: some of it may have escaped through the front of the head, which is broken off. The medulla is rounded at its free end, is distended and ﬁlls most of the head. Had this specimen lived it would probably have formed an anen— cephalic foetus. But in order to have lived through gestation the change in the whole embryo could not have been as -radical as it is in this specimen, and judging by the anatomy of anen— cephalic monsters the destruction of the brain does not, in all probability, begin until some time after the sixth week. In No. I42 the changes within the embryo are also extreme, but the remnants of the organs remain within the body. However, the external features of the embryo have vanished entirely, the arms and legs having atrophied completely.
No. 364, which belongs to this group, is a most remarkable specimen, for it forms a typical monster and is accompanied by an excellent history. The ovum, covered with a few ragged villi, is from a ﬁrst conception in a woman who had been married four years. It was from a natural abortion, the woman being very anxious to have children. In general, the woman appears to be healthy, but she has suffered from a variety of troubles with her uterus and vagina, which are given at greater length in the history of the case. The usual changes are found in the chorion, indicating faulty implantation and inﬂammation. The embryo, whose menstrual age is 99 days, corresponds in length with a normal embryo 40 days old, that is, having a menstrual age of 68 days. In other words, the pathological process in No. 364 has been under way for fully a month.
The large blood—vessels and heart are still ﬁlled with blood and there is a general inﬁltration of the tissues with round cells; the vessels of the umbilical cord do not reach to the chorion, showing that the nutrition of the embryo has been cut off entirely. There is a general destruction of the tissue due to, or causing, the irregular growth of the embryo. This is especially well marked in the brain and spinal cord, which are rudimentary, are converted into a mass of vascular connective tissue capped by a rudimentary shield of brain tissue, as is illustrated in the figures.
There is pronounced hare—lip, the ears are displaced, and there is exomphalos, spina biﬁda and pseudencephalus; the latter is no doubt the forerunner of anencephalus.
That the pathological conditions found in most of the specimens reported in this contribution are. not of germinal origin, but rather due to the changes in the environment of the ovum, as may be brought about by eudometritis, is illustrated beautifully by two sets of twins of the sixth week, which I have been fortunate enough to procure—one from Professor Brodel and the other_from Professor Minot. To these may be added the twins of the ﬁfth week (Nos. 330a and 33ob), the two sets of specimens, each from the same woman (Nos. I10 and I4I and 308 and 325), kindly sent me by Drs. West and Ballard. These groups of specimens speak volumes against the germinal theory of merosomatous monsters. The facts of the case have been discussed under a special heading above, and they need not be repeated here. However, if the law of probability and the normal condition of the embryos in earlier pregnancies were not taken into consideration, they could be explained by the germinal, just as well as by the environmental theory. The conclusive evidence in favor of monsters being due to a change in the environment, which causes faulty implantation of the ovum, thus impairing the nutrition of the embryo, is found in the study of the embryo in tubal pregnancy, where 96 per cent of them are monstrous. Were the primary trouble in the germ, no more pathological ova should be found in tubal than in uterine pregnancies. Furthermore, all this is vouched for by comparative experimental teratology.
To be sure, polysomatous, pansomatous and those merosomatous monsters that are due to an arrest of development at a very early stage (monopodia) and those variations of an hereditary nature (polydactyly, polymastia) and ordinary anatomical anomalies, cannot be due to changed environment at a stage so late as the fourth week of pregnancy, and some of them, like variations in the hands and feet especially, are markedly hereditary, and therefore germinal in nature. However, this digression is not altogether to the point; the merosomatous monsters, the subject of this report, are due to a direct experiment which is equivalent to the mechanical removal of most of the villi of the chorion.
The two sets of twins (Nos. my and 341) are alike in many respects, for each set is contained in a single chorion. The degree of development and degeneration is about the same for each set. In No. 207, the younger one, the process was severe but not of long duration, while in No. 341 the opposite must have been the case. In both sets the organs and tissues are well dissociated, showing the usual changes so often seen in the embryos studied. When I ﬁrst took up the study of pathological embryos I was inclined to the idea that the changes in the chorion were often of a secondary nature, but as the specimens became more and more numerous and were preserved better and better, which enabled me to study them with greater care, this idea had to be abandoned. Now it is clear that we are dealing with a simple experiment which must bring about the changes in the ovum and embryo to make it pathological. The greater number of ordinary abortions in the ﬁrst month consists of ordinary pathological embryos. The changes in them are so radical that it is impossible for but few of them to develop into monsters had they not been aborted. However, it is not difficult to imagine specimens in which the changes are not so extreme, that is, they are due to minor changes in the chorion, which may retard the development of a part of the embryo, and afterwards become corrected, thus favoring the growth of a distorted embryo into a merosomatous monster. In nearly all of these embryos there is a tendency for the liquor amnii to increase in quantity, a condition which must also be viewed as a secondary process, and, therefore, cannot be of fundamental signiﬁcance in the production of monsters.
It is evident from the study of pathological ova that in order to complete the chain of evidence it will be necessary to study anew and with much greater care the membranes of embryos which appear to be normal, for in them we shall no doubt ﬁnd the very earliest stages of monsters which could have existed and grown throughout pregnancy. The recent publication of Fischel, as well as the more careful study of some of my “normal” embryos (Nos. 6, IO, II, 12 and 80), indicates that embryos of this kind will probably serve to clear up entirely the subject under discussion.