Paper - A study of the causes underlying the origin of human monsters 3

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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

Lithium Embryos and Nodular forms in Chicks and in Man

Comparative teratology gives ample testimony to explain the production of double monsters, and it is now clear how they may be produced in man. But when the study is extended to merosomatous terata great difliculties arise in making comparisons between the large number of experimental monsters in lower animals, the pathological embryos which I have studied, and finished monsters at the end of pregnancy. The endless literature upon these subjects is very difficult to blend into a continuous story on account of the various terminologies used by the different writers. However, I hope to draw some satisfactory lines through it, being guided by comparative anatomy and embryology.

The immense number of experiments performed upon the eggs of different species of animals has given the greatest "variety of monsters of very irregular form, and extremely difficult to interpret properly in the light of our present knowledge of embryology. Quite recently our distinguished tera.tologist, Morgan, has presented this problem in a new light in his series of studies on the relation between normal and abnormal development of the embryo of the frog.‘ No doubt scientific investigations like these of Morgan will soon clear up many of the questions in teratology which have perplexed us so long. It may be noted that new kinds of monsters are constantly being produced by the experimental teratologist, one of the most interesting being that known as the lithium larva.

‘Morgan, Ten Studies in Roux’s Archiv, Vols. XV-XIX, 1902-I905.

In 1893, Herbst,2 while studying sea-urchins’ eggs, observed that the action of lithium salts upon them caused the layers of the blastoderm to invert in development. The lithium experiments were repeated by others, including Morgan, upon frogs’ eggs, who found that the upper protoplasmic contents of the egg fails to move downward, which is followed by a complete inversion of the germ layers. The entire upper part of the egg sinks into its interior and forms a medullary plate which is bent back upon itself. This change in development is due to the physical and chemical action of lithium salts, for it cannot be brought about by any other means.

Very recently Stockard3 experimented upon Fundulus with solutions of lithium chloride and produced monsters which developed into quite decent fishes, but at present it is impossible to compare them with lithium larvae of sea-urchins and frogs. In these embryos the blastoderm is usually prevented from growing downward over the yolk, as is also the case in the frog, and therefore bulges as a cap upon the upper part of the egg. In stronger solutions of lithium this cap often constricts at its borders and finally pinches itself off from the yolk and dies. In embryos which survive, the heart beats slowly, the eyes often fail to develop, the blood is colorless and therefore appears to lack hemoglobin. These characteristics, taken with the inability to recover from the lithium effect, seem to prove that they are due to chemical causes.

At present it is difficult to compare the great variety of monsters produced in anamniotic with those obtained in amniotic animals, for the number of the latter is relatively small and their description meager. We have a series of excellent papers on the production of monsters in the hen’s egg by Panum,‘ Dareste5 and Féré.° These authors, however, devoted their main discussion to the teratogenic agents, of which they used a great variety. In general, they employed variations in temperature during incubation and, although they produced many kinds of monsters, they never could predict which kind they were to obtain from a given batch of eggs. It is, therefore, very apparent why experimental teratologists did not make much headway as long as they experimented upon the chick. However, they did establish two facts: first, that monsters are produced from the hen’s egg by all kinds of external influences, as varnishing the shell, placing the egg in the vertical position, change of temperature, traumatic means, shaking, magnetic and electrical influences, by gases which penetrate the shell and by a great variety of chemical poisons ‘and toxines injected into the white of the egg. In general, any substance which either interferes with the nutrition of the egg or poisons it, causes the embryo to become abnormal, but a special kind of monster is never produced by a given teratogenic agent. In this respect the experiments upon anamniotic eggs are far more satisfactory.

'Herbst, Mitth. Zool. Sta., Neapel, 1893, and Roux’s Archiv, 1896. ‘Joni’. Ex. Zool., Baltimore, 1906.

‘Panum, Entstehung d. Missbildungen, Berlin, 1880. ’Dareste, Recherches sur la production de monstrosités, Paris, 1891. 'Féré, Cinquantenaire de la Société de Biologie, Paris, 1899.

Panum classified the monsters he produced into two great groups: (I) Those in which the whole embryo is involved, (2) those in which but part of it is abnormal. Under the first group there are (a) flattened forms, that is, the germinal area is not much changed in shape; (b) flattened forms with the production of red blood, i. e., only the embryo is affected; (c) cylindrical forms, the embryo becomes abnormal in a more advanced stage; and (d) amorphous forms. This first group, with its four subdivisions, may possibly be compared with the great variety of irregular monsters of which the lithium larva may be considered the type. At any rate, we may say that there is an analogy. Certainly there is a similarity between the cylindrical forms, which do not live long, and the deformed fishes obtained from Fundulus by means of lithium chloride solutions. The great change which has taken place in both varieties makes it impossible for either of them to exist for a longer time. A similar form of monster is also often found in mammals, and His, in adopting Panum’s terminology, has classed it with cylindrical monsters.

pathological changes in them are so radical that their lives are also short. Amorphous forms are analogous with lithium larvae and identical with the nodular form in man. In general, only part of the embryo continues to develop in an irregular fashion and finally the whole embryo dies. The flattened forms, with and without blood—vessels, are identical in man with the vesicular forms, that is, ova containing umbilical vesicles only, and to ova without embryos, respectively.

The merosomatous monsters in which the whole embryo is affected, total monsters as they are also called, are not likely to live long, but they are of great interest to those studying teratological problems. VVhile they are being formed a certain number of eggs develop into partial monsters, and in man some of them grow into foetuses which may go on to full term, and a very small number of them live on to maturity after birth.

The recent total monsters produced by Bardeen7 in subjecting the sperm of toads to X-rays before fertilization can be explained on the same ground as are lithium embryos. The tadpoles which develop from such eggs are entirely diseased, continue to grow in an irregular manner and appear much like lithium larvae in Fundulus or as ordinary pathological embryos in man. In all three cases the primary radical change involves the whole embryo; in Bardeen’s experiment the cause affected the sperm before fertilization, in Fundulus shortly after fertilization, and in human pathological embryos somewhat later. ‘ Although the methods employed are very different, the principle involved and the results obtained are much the same. V

A very large number of monsters are to be classed as total monsters. They are probably brought into existence by‘ a variety of circumstances, all of which interfere with the nutrition and growth of the whole embryo and the changes in them are so radical that their lives are very short. In man the primary trouble cannot be due to the presence of poisons in the blood of the mother, to correspond with chemicals used by teratologists in producing lithium larvae, for instance, nor to a fever, to correspond with the changes in temperature used to produce chick monsters. The process in man is quite different, being due probably to faulty implantation of the ovum, which naturally affects the growth of the embryo. This will be discussed under a subsequent heading.

'Bardeen, Jour. Ex. Zbo1., IV, 1907.