Paper - A study of the causes underlying the origin of human monsters 1

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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

Historical and General Historical

The changes found in the pathological embryos to be described in this memoir are so radical in nearly all specimens that it is almost useless to speculate regarding the fate of the embryos had they continued to grow to the end of a normal pregnancy. Could the circulation be maintained these specimens might have developed into amorphous monsters, a condition which is probable only when there is a normal twin foetus to supply the nutrition. In only one of my specimens (No. 87) are the possibilities for such a termination present. Here on one side of the chorion there is a normal embryo of the third week and on the other side a highly developed umbilical vesicle with but a rudimentary amnion, but no real body of an embryo. In all of the other twin specimens the changes in both embryos are radical and identical, so that we could not hope to have had the one embryo dependent upon the other for its circulation and nutrition.

In general then the changes in the embryo and its membrane, due to the inflammatory action in the uterus, are so great that if the ovum is not aborted at an early date (as it usually is) it is converted into a solid mole which in the course of time is likewise expelled. A few specimens, how~ ever, are but slightly changed, and these would probably have grown into some sort of merosomatous monsters had they been retained in the uterus. From my experience I am convinced that in the study of specimens like these we have the key by which we can unlock lhany of the mysteries of teratology.

‘The data here recorded are taken largely from Ballantyne’s Antenatal Pathology.

In my first two communications I carefully avoided all speculations on this subject, for I was well aware of the sad state this subject is in, and mere speculations would not help teratology out of its difficult position. However, what little progress has been made in the study of terata has been made by the embryologist and we naturally still have confidence in him. The course to be followed, therefore, is the study of early abortions, and this I have done diligently. I can, therefore, subscribe fully to what Ballantyne has recently said in his able and scholarly treatise on antenatal pathology. He says, page 77: “Now, in reference to the inquiry into the problems of teratology or embryonic pathology, let me emphasize the importance of a thorough scrutiny of the foetal membranes and of the routine examination, microscopic as well as macroscopic, of all abortion sacs and their contents thrown off in- the early months of pregnancy. What is most wanted at present are careful descriptions of monstrous embryos from abortion sacs’, observations upon teratological conditions while the organism is still in the embryonic period of antenatal life. These are essential for the further progress of a knowledge of human teratogenesis, and they are at the present time the desiderata of embryonic pathology. Microscopic human monstrosities are, as a matter of fact, almost unknown.”

The last sentence is hardly justifiable, for a pretty large number of young pathological embryos have been described by His, Giacomini and myself, but these do not resemble monsters at full term any more than an embryo of the fourth week resembles a new-born child. Whether the early pathological embryos are young monsters, or young monsters of so extreme a degree that they will not continue to grow, is now the most important question of the capital problem in teratology. I think that the specimens that are reported in this publication contribute to the answer of this question, but many more observations are required before the answer will be accepted by all teratologists.

The history of teratology co-exists with that of medicine and includes mythology, the vilest superstitions and scientific embryology. The medical profession have abandoned the idea of supernatural causes in the production of monsters No. 1.] ORIGIN OF HUMAN MONSTERS. II

and have gladly exchanged the hybridity theory (cohabitation with lower animals) for the more innocent one of maternal impressions. The last notion is of great antiquity, is of world-wide distribution and is intimately related to witchcraft. It is gratifying to note that these superstitions, based upon coincidences, have been raised from medicine by the study of scientific anatomy, and the more recent work by J. F. Meckel in this direction can be ranked with that of Morgagni and Virchow. Morgagni gave the first blow to humoral pathology by giving medicine an anatomical basis, Meckel cast out devils, witches and mother’s marks by placing teratology on an embryological basis, and Virchow won the third great victory for anatomy, probably the greatest contribution ever made to medicine, by giving it an histological basis. It would be inappropriate to enter any further into a discussion of teratogenesis in this publication, for in general the superstitious notions are abandoned by scientific physicians, although they may still be entertained by a few practitioners of some eminence. It is humiliating to state that these practitioners seem to reside exclusively in America, but we have every reason to hope that when scientific medical education becomes general with us they will also disappear.

Most of the great men who have contributed to the progress of medicine, from Hippocrates and Aristotle to the modern scientists, tried to ascribe the production of monsters to natural and not to supernatural processes. From the first the explanations were as satisfactory as they are to-day, for even now we barely do better than Aristotle did. However, the spread of the scientific spirit beginning with the study and practice of anatomy by all medical students has driven medical superstitions pretty well out of the medical profession. In this respect we differ from-the ancients. The first scientific explanations were of a crude mechanical nature, like those due to excessive lacing, malformations of the uterus or a twin foetus, which might injure the embryo. This notion was superseded in part by the theory of Morgagni, who maintained that monsters were due to foetal disease again received its death-blow from J. F. Meckel, who pointed out the well known fact that many structural anomalies are hereditary. This observation naturally divided terata into two groups: those which are hereditary and germinal, and those which are not hereditary but due to mechanical injury or disease. I think this line of division should be drawn much sharper than it is, but until our data can be arranged better than is now possible we are still quite uncertain regarding a large number of terata. It seems to me that many merosomatous terata (all kinds of anatomical anomalies and variations of the extremities, like polydactyly and possibly some cases of arrested development like ectrodactyly and hare—lip) are germinal and cannot be produced experimentally. Other monsters in which more or less of the foetus is destroyed, as in iniencephaly, spina bifida, aneucephaly, cyclopia, club-foot and many varieties of arrested development, are not germinal but are produced in some mechanical way which usually interferes with the nutrition of the embryo. In my notes I have been in the habit of calling those belonging to the first group as being abnormal and those to the second group as pathological. The one is germinal with a hereditary tendency, and the other is acquired and therefore not hereditary; polydactyly is inherited, cyclopia is not, although there seems to be a tendency for it to occur more than once in abortions from the same woman. However, if this is true, it may be due to the same cause in the uterus of the mother affecting the nutrition of successive ova, thus producing similar deformities in the embryos. Usually a woman who gives birth to several monsters has the varieties mixed up pretty well, the first may have hydrocephalus, the next hare-lip and the third cyclopia. Reducing it to a matter of chance, a woman who has given birth to one monster is more likely to give birth to a second one, which, however, is rarely like the first. In experimental teratology in birds and amphibia the result is the same. Here monsters may be produced experimentally with a variety of agents, even by treating the semen of toads with X—rays, but the variety of monster can never be predicted, and if there are a number of them they are usually of -mixed types.”

What I have to say in this publication of monsters applies only merosomatous terata which are not of an hereditary nature and are no doubt produced by agents which interfere with the nutrition of the embryo. Having taken only those monsters from which the germinal factor is excluded, it makes it necessary once more to consider some minor mechanical agents as their cause, which may be termed a modified mechanical theory.

The advocates of the mechanical theory gradually lost ground, for they had to combat the germinal theory on the one hand, and on the other they were compelled to state that mechanical influences, generally those due to lacing, caused the foetus to become monstrous by the pressure that was exerted upon it. The theory was then modified to include primarily intra-abdominal influences like tumors, malformations of the pelvis and uterus, as well as those within the ovum itself. Gradually we see less and less weight placed upon any of these specific causes, and finally the modern advocates of the theory believe that amniotic bands and adhesions are the main influences in the production of monstrosities. It is needless to state that each advocate had his own combination of circumstances, and when all of them are taken together, with modifications and exceptions, it is practically impossible to make general statements. Suffice to say that the objections to each form of the theory appear to be sufficient to explode the whole theory, and to the bulk of physicians maternal influences seem to be as rational a cause in the production of monsters as mechanical influences, for the data of experience are about as good in the former as in the latter.

There are some rare cases of spontaneous amputation of the extremities which are said to be due to pressure of the umbilical cord. However, these cases can be separated into two marked groups, one in which there is an actual amputation and the other in which there is an atrophic or rudimentary hand or foot attached. In the latter instance it seems to me that it is very irrational to hold the umbilical cord responsible for the amputation. Furthermore, the cause is possibly germinal, as may be the case in sympodia, syndactyly and ectrodactyly. The rare cases in which there is actual amputation of the extremity are more likely to have been produced by mechanical injuries during labor than by having the amputated limb caught in a loop of the umbilical cord. In fact, we must admit that we are unable to explain by any satisfactory hypothesis either congenital amputations or dislocations.

'Bardeen, Iour. of Experimental Zool., 1907.

It has been noticed occasionally in merosomatous monsters that the diseased or malformed part is tied by means of bands of tissue either to the amnion or to adjacent parts "of the body of the foetus. These observations, relatively few in number, have led to the theory that the bands caused the deformity. It seems to me that, in view of the idea that many monsters are due simply to an arrest of development of some part of the embryo, that hydramnios is usually present, and that all kinds of monstrosities may be produced in lower animals (including amphibia which have no amnion), it is highly probable that amniotic bands and the like are secondary in their formation and have nothing whatever to do with the production of monsters. The more the embryo» logical theory is tested by experimental methods the more all simple mechanical explanations suffer, and it seems to me that all of them will have to be abandoned.

It is not especially remarkable to find that when the head or face is malformed the diseased part occasionally forms a secondary attachment with the amnion; or that, as in exomphalos, where the umbilical cord is “dilated,” the extruded viscera come in direct contact with the placenta, as they should, and the blood-vessels are scattered and run along the amnion to the placenta, as should also be the case when the subject is viewed from the standpoint of embryology. Furthermore, deformities of the extremities are of frequent occurrence, but amniotic bands are rarely found, and when they are present they are often attached to the body of the embryo and not to the deformed extremity. It seems to me, therefore, that as facts accumulate it becomes clearer and clearer that the occasional amniotic adhesions found are due to the presence of the monster and are not causal in nature.-3

Possibly I have devoted too much space to the discussion of mechanical theories in teratogenesis. What has been said is no doubt acceptable to all embryologists, and my apology is due to the fact that the influence of maternal impressions upon the offspring is still believed in by so large a number of American medical writers of note and that mechanical notions regarding embryology are entertained by physicians in general.

The great embryologists from Harvey onward explained the conditions found in monsters as due to an arrest of development, for they saw in these distorted individuals conditions which are normally found in the embryo. The embryological theory was first well formulated by J. F. Meckel, who explained the beast—1ike appearance of some monsters by the fact that in his development man passes successively through stages found in lower animals. To those who have accepted the doctrine of evolution this is all clear, but it remains to be shown what are the factors in development, and the effect of changes in the embryo upon the growth of the foetus.

As has been pointed out above, we must divide monsters into two groups, those in which the proper conditions to produce them are already in the germ (are therefore inherited), and those due to certain external influences which act upon the egg after it is fertilized. It is obvious that only the second group can be considered in any experiments made upon the embryo. So, if the pathological ova I have studied are all due to a diseased chorion, which in turn is dependent upon endometritis, then we should find embryos tending towards club-foot, anencephaly, iniencephaly, spina bifida and cyclopia, which in fact proves to be the case. However, a large group of new monsters, known only to embryologists, make their appearance and from the very nature of the abnormality found but few of them could develop beyond the first months of pregnancy. In their study comparisons have been constantly made with normal embryos of the same size, and in this way, to a certain degree, it is possible to picture the order of events. It is found that in these specimens some tissues are more susceptible than others, and when the nutrition of the ovum is impaired it is these that are affected first. In very early stages the amnion and embryo are equally susceptible and the umbilical vesicle and chorion are the most resistant. Later it is the embryo alone, and still later the head, central nervous system and extremities. It follows then that the parts most susceptible are those most frequently found changed, or wanting, in merosomatous nongerminal monsters. In general the varieties found in my collection of young embryos correspond with those obtained experimentally by others in birds and appear much like the most common human monsters.

'Ballantyne says: “The reader may feel (and he is justified in so feeling) that, after all, experimental teratogeny has not done much for the understanding of the mode of origin of monstrosities, if it has weakened a belief in the influence of the amnion.” I may add that this argument can be applied to maternal impressions as a cause equally as well.

The Saint-‘Hilaires, who contributed so very much to our knowledge of teratology, were the first to study the subject experimentally. By a variety of experiments made upon the shell of the egg (e. g., pricking and varnishing) the older Saint-Hilaire produced a large number of anomalies in which there were defective heads and spina bifida. His experiments were made upon eggs after development was well under way, and his results were pronounced enough to allow of comparison with human monsters. The younger Saint-Hilaire extended the experiments to include the earliest days of incubation, and found that the embryos which developed were dwarfed or were wanting altogether. In no instance were polysomatous monsters produced. At any rate, the experiments of the Saint—Hilaires show that a change in the external physical conditions may influence and modify normal development and thereby produce a variety of merosomatous terata.

During the following seventy-five years a great amount of experimental work was done upon chicks by numerous investigators, which showed that the varieties of monsters produced were quite constant, no matter what agent is used, but no single variety could be produced with certainty. It was found impossible to experiment with precision, for a certain per cent of eggs would produce one or more varieties of deformed embryos.