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) J Morphol. 19: 3-368.

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A Study Of The Causes Underlying The Origin Of Human Monsters

Historic Disclaimer - information about historic embryology pages

Pages where the terms "Historic" (textbooks, papers, people, recommendations) 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, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

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.

Experimental.

Recent Work Upon the Production of Polysomatous Monsters.

The various theories regarding teratogenesis which had troubled mankind for so many centuries were finally exploded by naturalists, whose speculations gradually led them to experiment upon this subject. Anatomists and zoologists had deduced that the primary change lay in the egg about the time of fertilization, and we read in J. Muller,’ Valentin’ and Leuckart3 that a double monster is due to division of the embryo—forming substance in the earliest stage of development. The experiments subsequently made by Gerlachf Panum‘ and Dareste° upon chicks were negative in this respect, but the tradition has come down to us that polysomatous monsters are produced by a process of splitting of the primitive streak. The more recent anatomists—Fol, Rauber,

‘Muller, Meckel’s Archiv, I828.

‘Valentin, Handwiirterbuch d. Physiologic, I, 1842.

‘Leuckart, De Monstris, Giittingen, I845.

‘Gerlach, Doppeln-iissbildungen, I882.

‘Panum, Entstehung der Missbildungen, 1860.

‘Dareste, Recherches sur la production dc monstrosités, Paris, 1891.. 18 MALL. [VoL. XIX.

Born and O. Hertwig—who observed the developing egg and experimented upon it, were at first inclined to the theory that the first cause in the production of monsters is due to polyspermy, but this has not been substantiated.

The first reliable and valuable observations upon the production of double monsters were made by Vejdovskyf’ who noticed that the eggs of Lumbricus produce more monsters in warm than in cool weather, and he expressed the suspicion that they were produced by the change in temperature. Driesch“ seized upon this idea, experimented upon sea-urchins’ eggs, and found by subjecting them to high temperatures that the cells, in the two—cell stage, separated, each growing into an individual, but, however, remaining connected with each other. Driesch had already shown that when the blastomeres of these eggs are fully separated by shaking, each grows into a whole embryo, and it was now clear to him that double monsters are produced by separating the blastomeres slightly, but still keeping them close enough together so that the independent embryos grow into each other’s bodies to form a double individual.

By a very different method double monsters were also produced by Loeb.° He subjected sea—urchin eggs to an equal mixture of sea-water and distilled water shortly after they had been fertilized. The rapid absorption of water caused many of the cell membranes to burst, and part of their protoplasm escaped, which, however, remained connected with that inside of the membrane. All this took place before the nucleus had divided. Upon returning the eggs to normal sea-water cleavage began, and one of the first two nuclei wandered into the extruded protoplasm. Each nucleus with its protoplasm then became an embryo, and in case the embryo within the egg was not separated from the extra-ovate embryo by its active movements in the blastula and gastrula stage a double monster or “Siamese” twins were formed. Frequently they became separated and independent animals developed. It often happened that the outflow of protoplasm was multiple, and then the three, or even more, protoplasmic drops which were formed developed respectively into triple or quadruple monsters.

’Veidovsky, Entwicldsg. Untersuchungen, Prag, I890.

‘Driesch, Zeit. f. wiss Zool., LV, 1892.

'Loeb, Biological Lectures at Woods Hell, 1393: Pfliigex-'s Archiv, LV, 1894; Roux’: Archiv, I, 1895; and Studies in General Physiology.Chapter X, Chicago, 1905.

These important discoveries were soon extended to the vertebrates by E. B. Wilson,1° who experimented upon the eggs of Amphioxus, and by O. Schultze,“ who experimented upon those of the frog. Wilson partly separated the blastomeres of Amphionus in the two-celled stage and produced a variety of double monsters which developed until the first gill-slits were formed. In the gastrula stage almost every possible transition occurred between forms slightly expanded laterally to those in which the two bodies were joined only by a slender bridge of tissue. Incomplete separation of the blastomeres in the four-celled stage gave rise sometimes to double embryos of equal size, triple embryos, one being as large as the other two, or rarely to quadruple monsters. Wi1son’s studies prove, he believes, “that the unity of the normal embryo is not caused by a mere juxtaposition of the cells, but they indicate that this unity is not mechanical but physiological, and point toward the conclusion that there must be a structural continuity from cell to cell that is a medium of coordination, and that is broken by the mechanical displacement of the blastomeres.”

Oskar Schultze produced monsters in frogs by fixing the eggs between two glass plates, and after they had developed to the morula stage the plates were inverted. A number of the eggs righted themselves, but others grew into double embryos. Wetzel” extended the observations of Schultze and showed that there was a flow of protoplasm in each of the blastomeres into their upper hemispheres, which may account for the separation of the primary cells, thus laying the foundation for two embryos instead of one.

"Wilson, Iour. of Morph., 1893. “O. Schultze, Verhandl. d. anat. Gese11sch., 1894, and Roux’s Archiv.

I, 1895. "Wetze1, Arch. f. mik. Anat., XLVI, I895. 20 MALL. [VoL. XIX.

Spemann” has also produced polysomatous monsters from the frog’s egg by tying a ligature loosely around it in the twocell stage between the two blastomeres. Specimens in which the ligature struck the median plane of the embryo produced two-headed monsters of all grades, their development depending somewhat upon the degree of the mechanical constriction. He performed similar experiments upon Triton eggs, and in some instances found cyclopia in one or both of the heads. By broadening the anlage of the tail through splitting, a double tail may be formed, or in case limb-buds are divided one or more times two or even a cluster of limbs may be produced where but one develops normally.“

The experiments enumerated above, although not quite to the point in the present study, are reviewed because they show that teratogenetic problems are solved by experimental embryology and because they are very striking. If it is clear that polysomatous monsters are produced experimentally with such precision, the great variety of merosomatous terata of the experimenter must be admitted worthy of careful study. It is necessary to state this because only a small per cent of them live for some length of time, but they show a great similarity with early stages of human terata with which we are familiar. A glance at the great works of Dareste and Panum makes it clear that the deformed embryos they obtained are not easily interpreted and they could easily be pushed aside as not bearing upon the subject in question. The same criticism may be made against early pathological human embryos. That it is difficult to see any marked relation between them and monsters at the end of pregnancy caused me much confusion for a long time, but after studying a large number of deformed embryos I am finally convinced that the pathological embryos are nothing but young monsters. This conclusion is supported especially by the numerous investigations in experimental embryology, many of which are also at the same time investigations in experimental teratology. For this reason I shall consider briefly the recent work upon the production of merosomatous monsters.

”Spemann, Stizungsber. d. phys.—med. Gesellsch., Wfirzburg, I900; Zool. Jahrbuch, VII Supplementband, I904.

“Tornier, Roux’s Archiv, XX, I905.