Paper - A study of the causes underlying the origin of human monsters 7

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Mall FP. A study of the causes underlying the origin of human monsters. (1908) Jour, of Morphol., 19:

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1908 Mall TOC: Historical | Double Monster | Lithium embryos | Salts of potassium and heart | Spina bifida and anencephaly | Cyclopia and club-foot | Pathological ova | Twin pregnancies | Unruptured tubal pregnancies | Ruptured tubal pregnancies | Amnion Destruction | Moles | Pathological ova umbilical cord and amnion | Second week | Third week | Fourth week | Fifth week | Sixth week | Seventh week | Eighth week and older | Specimens and figures | Plates | Historic Papers | Franklin Mall

A Study Of The Causes Underlying The Origin Of Human Monsters

Pathological Ova

As we pass up the vertebrate scale it becomes more and more difficult to ascertain the primary causes which produce pathological ova, and presumably monsters. In fact, the causal study of teratogenesis has been and still is one of the capital problems in medicine which is gradually being solved by anatomists. It has been stated repeatedly in this paper that the missing link to complete the chain of evidence is to be found in the careful study of aborted ova which are found to be more or less diseased. In the excellent monograph by Granville‘ we find a report of the study of forty-five aborted ova, from which he concludes that the chorion is first diseased, which naturally results in retarding the growth of the embryo. He 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 an excess of hemorrhage.


I have been unable to obtain valuable data regarding the condition of the uterus in early abortions from pathological, gynecological or obstetrical literature. It is all clouded in mystery, and one finds an endless contradiction of opinions. It seems to me that a study of the norm, uterus and chorion is required before much headway can be made. In my opinion, this is possible only in some great clinic which has attached to it a first-class laboratory manned by able investigators. However, for the present, we must do the best we can with the data at our disposal. First, I shall quote from several competent recent writers.


‘Granville, Graphic Illustrations of Abortion, London, 1834.


Ahlfeld states in his treatise on obstetrics’ that many abortions are due to endometritis, which produces inflammatory adhesions of the placenta and membranes; hypertrophy of the decidua is associated with abnormal forms of the placenta, which is followed by an arrest of the development of the embryo. Furthermore, atrophic endometritis is commonly followed by the formation of an atrophic decidua, which in turn must retard the growth of the ovum. In addition to these forms there is a condition known as hemorrhagic endometritis, due to a variety of infections. The hemorrhages which take place in the chorion or placenta are often accompanied with bacteria or may be due to nephritis, which may be followed by decidual infarctions and death of the embryo. In these cases the effused masses of blood are in successive layers of old and new clots, forming a tumor known as decidua tuberosa. In case the bleeding continues after the death of the embryo the chorion may be converted into a fleshy mole.

Ahlfeld further states that repeated abortions are due to endometritis or to syphilis, but the second abortion need not by any means be due to the same cause as the first. If due to syphilis successive abortions occur later and later in pregnancy. Syphilis, and possibly gonorrhoea, causes abnormal development of the decidua; in chronic endometritis the decidua undergoes diffuse hypertrophy. According to Virchow, syphilis causes knotty development of the decidua in case the mother is infected; in case the father is infected the primary change is found in the chorion.

‘Ahlfeld, Geburtshilfe, I903. so MALL. [VoL. XIX.

According to Williams“ “the death of the foetus is frequently due to abnormalities in the development of the embryo which are inconsistent with foetal life. More often, however, it results from changes in the foetal appendages, which interfere with its nutrition, such as excessive torsion of the cord, producing hydramnios, hydatidiform mole or syphilis.


Abnormalities of the generative tract likewise play an important part in the etiology of abortion. Thus developmental anomalies of the uterus, or imperfect development of the normally formed organ, may be responsible for conditions which are unfavorable for the implantation of the ovum and later for the development of the placental circulation. Chronic metritis is supposed to act in the same way. . . . The most important factor in the production of abortion is afforded by diseases and abnormalities of the decidua. In hypertrophic forms of decidual endometritis—decidua polyposa—the bulk of maternal blood brought to the placental site goes to nourish the hyperplastic decidua, while in the atrophic forms the conditions are unfavorable for the normal implantation of the ovum and the development of the placenta. More important still is the part played by chronic glandular endometritis and acute inflammation of the decidua, The former is usually acompanied by hemorrhagic changes, and is the most frequent cause of abortion in the early months.‘


I gather from conferences with competent scientists of large experience that “uterine scrapings after abortion rarely show signs of endometritis, although they contain many leucocytes and characteristic masses of fibrin. When the abortions from one woman are frequent she is undoubtedly syphilitic.” Another argues that endometritis rarely shows the presence of inflammation, and states further that inflammation of this organ is usually confined to the cervical canal. Still another states that endometritis, which is a rare affection, is usually due to the gonococcus or sometimes to an acute infection. At this place it may be pertinent to state that pathological ova and monsters, which are quite frequently found in other mammals, cannot be due to syphilis or gonorrhoea, but are often accompanied with a peculiar kind of separation of the chorion. In such specimens a large mass of mucus and no blood encircles the ovum, and from all indications the embryo has died suddenly, for it is not deformed. It is not necessary to introduce more opinions, for they will not lead us nearer to a solution of the problem. For the present, the opinions as expressed by Ahlfeld and by VVilliams are the best at our disposal. Both are able scientific obstetricians, Ahlfeld being in addition a teratologist, and Williams a leading obstetrical pathologist.

‘Williams, Obstetrics, New York, 1903, p. 522.

‘Marchand, writing on moles, says in Eulenberg’s Encyclopedia, Vol. 15: “Abortives Ei ohne Spur eines Embryo oder mit mehr oder weniger unbekanntlichen Resten derselben. Ein sehr héiufiges Vorkommniss bei Aborten, welche wohl in den meisten Fallen durch friihzeitige Unterbrechung der Ernihrung infolge beginnender Lfisung des Eies von der Uteruswand, Blutungen in der Decidua basalis und capsularis oder durch vorausgehende Erkrankungen der Uterusschleimhaut bedingt ist. Zuweilen findet sich ein knotchenformiger Rest des Embryo an der Innenfléiche oder ein Rest des Nabelstranges oder .eine mit Fliissigkeit gefiillte Blase. Ist der Embryo nicht vollstandig zu Grunde gegangen und erfolgt die Ausstossung des Eies nicht, so kiinnen anderweitige Missbildungen die Folge sein. Bei der Ausstossung findet man die Decidua basalis und capsularis mit Blutextravasaten durchsetzt (Blutmole).”


It is well known that a woman who aborts a pathological ovum or gives birth to a monster will probably abort again, and runs a greater chance of giving birth to a second monster. Teratologists are inclined to read these facts in favor of the germinal origin of monsters, which may even be hereditary. Since there is no recorded case of a woman giving birth to a second polysomatous monster, while there are numerous cases in which women bore second merosomatous monsters, we can as well consider the former as “accidental” and the latter as due to some change in the uterus and not inherited through either the germ or the sperm. (Certain varieties like those of the extremities and anatomical anomalies must be excluded from this discussion, for they are known to be germinal and are hereditary.) To be sure, we cannot exclude the possibility of a certain per cent as being germinal, that is, there was some change in either of the germs before fertilization took place. On the other hand, experimental work on amphibian, fish and bird embryos shows that monsters can be produced with ease from perfectly normal fertilized eggs. In general the methods employed by experimental teratologists is to subject the eggs to various insults which affect the nutrition and impair the growth of the embryo. If now a similar condition can be found to exist for human pathological ova which corresponds with those the experimental teratologist produces, the point is proved, that is, many merosomatous monsters may be formed by placing normal ova into an unfavorable environment. All of our experience in teratogeny, if read aright, indicates that the normal ovum got into a diseased uterus did not implant itself well, and the consequent impairment of nutrition produced a monstrous embryo. This hypothesis, which will be proved to be correct under the heading of tubal pregnancy, explains fully the presence of so many pathological embryos in multiple abortions and the apparent germinal origin of merosomatous terata like spina bifida and anencephaly.


His,[1] in the discussion of normal and abnormal embryos, is rather of the opinion that pathological embryos are due to primary changes in the germ, and that their abortion naturally takes place because such ova act as foreign bodies in the uterus. In some instances, however, he excludes the possibility of the primary cause being due to an interference with their development, such as may be brought about by deficient nutrition, lack of oxygen and mechanical influences due to the uterus being displaced. Later,“ in a discussion of open questions in pathological embryology, he seems to be inclined to abandon the theory of the germinal origin of pathological ova altogether, for the examination of several specimens showed that the changes within them were of a secondary nature. They indicate that the embryo is in process of dying, that is, the tissues of an embryo as normally formed have become swollen, are disintegrating and strange cells are wandering through them. In His’s opinion such changes cannot be viewed as primary, but rather as secondary conditions.


The other student of pathological embryology, Giacomini," emphasizes the necessity of studying the form and structure of the decidua in normal as well as in pathological ova, for at this point mechanical and nutritive influences must occur, which are of prime importance in the production of early pathological embryos. He predicted that such a study, together with experiments upon lower animals, would ultimately explain the origin of monsters.


There is one more opinion, from the hundreds upon this subject, which I must not omit. It is from O. Hertwig,8 in his more or less general article on the production of spina bifida in Axolotl. After stating that a .6 per cent solution of NaCl will produce spina bifida in frogs and a .7 per cent solution will produce the same kind of monster in Axolotl, he asks whether it is not possible that some similar method is employed by nature to produce spina bifida ‘in man? Is it not possible for chemical substances in the b1ood—as alcohol, toxines or medicines—to pass from the uterus to the ovum and make it monstrous? Evidently he believes that the power to become monstrous is not inherited, but is due to external influences.

It is extremely difficult, if not impossible, to prove directly that the primary changes which produce pathological ova are in the chorion and not in the embryo. I find in glancing over the tables which follow, with the discussion of the individual specimens, that among 143 pathological specimens but fifteen appear to have a normal chorion, and that in thirty-five the chorion is sufficiently infiltrated with leucocytes to indicate that some inflamamtory process was present in the uterus. In all of the specimens excepting the fifteen in which the chorion appears to be normal all kinds of secondary changes have taken place. The mesodern is fibrous, hyaline or oedematous, the villi are atrophic, hypertrophic or missing altogether, and the syncytium is irregular or necrotic, and sometimes it has attacked and invaded the mesoderm of the chorion. The decidua when present is usually infiltrated with leucocytes, which often accumulate in great masses, or often form abscesses. All this could take place if the embryo had died and the ovum had continued to grow, but on account of the presence of a dead embryo the uterus reacts as if it had a foreign body to expel. In fact, most of these changes just enumerated probably took place long after the embryo had become monstrous, and we are no doubt treating with the primary process, much intensified by the presence of a pathological ovum. The final proof in favor of the theory that these changes are primary will be given under the discussion of tubal pregnancy.


'Giacomini, Merkel u. Bonnet, Ergebnisse, IV, 1894. '0. Hertwig, Gegenbaur’s Festschrift, II, 1896.


It will be noticed that the “normal” chorion is most common in young ova, that is, before the process of destruction has been under way for a long time. In an earlier publication” upon this subject I was much inclined to the idea that the primary difficulty in a pathological ovum is to be sought in the embryo, but later” I formed the specimens into two groups: (1) Those in which the primary cause lies in the embryo, and (2) those in which it is outside of the chorion. This gradual change of my ideas is identical with that which both His and Giacomini passed through, for all of us based our conclusions upon a simple morphological study. The morphologist must be very careful in the arrangement of his sequences, and I think it is to our credit that we have been so. But now, since we have experimental teratology and a. more careful study of the gynecological history of the speci mens to fall back upon, it seems to me that the solution of the problem is at hand.


‘Mall, Welch Festschrift, J. H. Hosp. Rep., IX, 1900. "Mall, Vaughan Festschrift, Ann Arbor, 1903.

The ova which appear to be normal, but have within them deformed embryos, or none at all, are the ones that require our most careful consideration, for in them we are to find the first pathological changes. In studying the villi of the chorion in these specimens I tried to remain on the safe side when I stated that they were fibrous or oedematous, and no doubt erred correspondingly when I stated that others were normal in structure. In the course of time I found that in most chorions which were markedly pathological a stringy mass of fibrin or mucus more or less rich in leucocytes was found between the villi. In specimens undoubtedly normal and containing a normal embryo this stringy mass was never found. Occasionally a stringy mass was found between the villi in ova which appeared to be perfectly normal. A good example is found in an ovum which appeared perfectly normal with the exception of a lateral pouch to it, containing an embryo four millimeters long which is slightly deformed“ (No. 80). Sections of the villi show that they are perfect in form. and in structure, being covered with a well-developed syncytium. Between the villi there are strands of a fibrin—like mass, in which there are imbedded a number of leucocytes. Another specimen which has been described by me as a normal one contains a similar substance between its villi” (No. 12). In this specimen there is an unusually well developed magma reticulé and the head is underdeveloped. The neural tube is wide open at both ends, and it seems to me that its form is not quite normal. It came from a woman twenty-three years old who had been pregnant twice, aborting both times. Two other specimens may be mentioned, one which I have also described as a very young normal ovum because I knew that the abortion had not been a natural one.” The woman had had a continuous hemorrhage for seven days before the abortion, and since then I have learned that the detachment of a normal ovum for a much shorter time than seven days is suflicient to cause an embryo to become monstrous. Specimen No. 250 of this communication is about as old as No. I2, only it is slightly more deformed. It had been removed with‘ a curette from a woman who was suffering from uterine trouble. The decidua which encircles the ovum is well infiltrated with leucocytes, showing that the decidua was inflamed. These four specimens are representative. One was detached by mechanical means, one was removed by a curette on account of endometritis, and two were spontaneous abortions of ova which appeared to be normal but contained a stringy mass between the villi. This condition is usually well marked after the chorion has undergone radical changes and is well infiltrated with leucocytes, which often form into small abscesses.


“Mall, Johns Hopkins Hospital Reports, IX, Fig. 80. ”Embryo No. 12, Journal of Morph., X, 1897, Arch. fiir Anat., Suppl. Bd., 1897, Johns Hopkins Hospital Reports, IX, Fig. I2. “No. II, Anat. Anz., VIII, 1893, Journal of Morph, X, and Johns Hopkins Hospital Reports, IX, Figs. 14 and I5. 56 MALL. [VoI.. XIX.


In the following table I have brought together all of the pathological ova in my collection in which there is any history of the women from whom they were obtained. Positive as well as negative histories are given.

A glance at this table shows that in eleven, cases the main trouble preceding the abortion was a severe hemorrhage extending over a number of days. In a second set of twelve cases the abortions were from first pregnancies in women newly married or who had been married for some time and were anxious to have children. In the third group of ten cases the women had given birth to a number of children and then began to abort, often a second or third time. The first group need not be considered further, but the second group consists of women who are naturally sterile and abort when they become pregnant. The third group of ten cases is more easily understood. The women, perfectly healthy, gave birth to one or more children and then conceived but aborted quite regularly. In these cases we must admit that the uterus was at first perfectly healthy and -the ovum was normal, but later, due to a variety of infections, the uterus became “inflamed,” and thereafter the fertilized ovum could not implant itself, became pathological, and later was aborted. According to the data given, seven of the mothers were healthy and twelve had uterine disease. Although this division does not correspond with the above three classes, in a general way it is suggested that women who are called normal abort with much hemorrhage, while the ones with uterine disease belong to the second and third classes mentioned above. Although these data indicate that pathological embryos are due to faulty implantation of the ovum, they by no means prove it. All of the ova in the third group of ten cases could certainly not have been destined to become pathological, for they all came from women who had given birth to healthy children. They could not attach themselves successfully to the diseased uterus, and, due to malnutrition or poisons which are thrown out from inflamed surfaces, the chorion became pathological and the embryos deformed. This point is fully proved, I believe, in the study of ova from tubal pregnancies.


No.

No. Condition of Mother. Remarks.

11 Apparently normal. Some Hemorrhage for 7 days.

r2 Married 3 years. None Two abortions.

32 . . . . . . . . . . . . . . . . . . . . . . . . . . . ? Hemorrhage 4 days.

58 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . First pregnancy.

70 . . . . . . . . . . . . . . . . . . . . . . . . . . . r Great flooding.

71 Chronic cystitis and endome- None First pregnancy, gave birth to

tritis. a child a year later.

87 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Hemorrhage for :2 days.

no Uterus large and retroverted. 9 Hemorrhage 5 days. See No.

41. 122 . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hemorrhage 8 days.

133 Perfectly normal. . Hemorrhage 8 days.

134 . . . . . .. . . . . . . . . . . . . . . . . . . . . . . Mechanical injury to ovum.

14: Uterus large and retroverted 9 See No. no.

I42 . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Hemorrhage 4 days, third abortion, one 3 mos., and one 20 mos. ago.

152 Endometritis, Some T h ird successive abortion, each time in third month.

159 Perfectly healthy father and None Married two years. This is

m o t h e r . No indication second abortion at third

whatever of endometritis. month. Repeated hemorrhage during pregnancy. Anxious to have child.

16: Purulent leucorrhoea. Had ?

tube introduced 4 weeks

before abortion.

162 Not the slightest indication of 5 Bleeding for two weeks before

uterine disease. abortion.

no 5 Syphilis suspected. None Married three months.

209 30 years old. ? Three years ago miscarriage in third month and 3 months

I ago gave birth to a monster.

226 . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 . . . . . . . . . . . . . . . . . . . . . . . . . .

228 Fairly healthy. None First pregnancy.

2 3:) Always menstruated regularly 3 Three other miscarriages.

during pregnancy.

246 Youngest child 7 years old. 2 Five miscarriages, all about

Since then miscarriages. the same size as this one.

2 5o . . . . . . . . . . . . . . . . . . . . . . . . . . . ? From uterine scrapings.

252 First pregnancy in an un- None Continuous hemorrhage for a

married woman. month.

278 Chronic endometritis. P From uterine scrapings,

292a Was curetted two years ago None First pregnancy.

for menorrhagia.

297 . . . . . . . . . . . . . . . . . . . . . . . . . . . ? From uterine scrapings.

. . . . . . . . . . . . . . . . . . . . . . . . . .. }FmmtheSameW0man_ 330 . . . . . . . . . . . . . . . . . . . . . . . . . . . None One other abortion in eighth month.

364 Uterine trouble. None First conception in a woman anxious to have a. child.

395 Removed o n a c c o 11 n t o f ? From uterine scrapings.

eclampsia.

399 Woman a marked bleeder. None Married ten months.

402 Subinvolution of the uterus. 2 58

  1. His, Anatomic menschl. Embryonen, II, 1882. ‘His, Virchow Festschrift, I, 1899.