240 CARNEGIE INSTITUTION OF WASHINGTON. 



Further Experiments Aiming at the Control of Defective and Monstrous 

 Development, by E. I. Werber. 



Starting from the hypothesis that the origin of monsters is due to parental 

 metabolic toxemia, experiments were carried out by the writer at the Marine 

 Biological Laboratory at Woods Hole during the summer of 1914 on fertilized 

 eggs of the marine teleost Fundulus heteroclitus, which were subjected at the 

 early cleavage stages to the influence of solutions in sea-water of some sub- 

 stances found in the blood or urine respectively of man during certain distur- 

 bances of metabolism. With only two of these substances, i. e., with butyric 

 acid and acetone, definite and positive results have been obtained; a very 

 great variety of monsters having been recorded/ which are strikingly analogous 

 to the well-known monsters found in man and other mammals. 



These experiments were continued and extended in the summer of 1915 with 

 a view of testing the action of other toxic substances of pathologic metabolism 

 on the teleost egg as well as of ascertaining, if possible, the mechanism of action 

 of substances experiments with which have yielded the interesting results 

 recorded in the work of the preceding year. 



No definite data have as yet been obtained for the action of lactic acid, 

 ammonium acetate, and ammonium benzoate, which have been employed in 

 some experiments of this year. It seems unlikely, however, that any one of 

 these substances might be responsible for defective development in nature ; for 

 solutions of them are practical^ harmless up to a certain degree, beyond which 

 they are so highly toxic that eggs which are subjected to their action are killed 

 at a very early stage of development — viz, before the formation of the embryo. 



The repetition and extension of the successful experiments of 1914 — i. e., 

 with butyric acid and acetone — afforded, however, a very good opportunity for 

 studying the mechanism involved in the action of solutions of these substances 

 in causing Fundulus eggs to develop in a monstrous manner. Thus it has so 

 far been found that toxicity of the medium and increased permeability of the 

 eggs' membrane which calls forth an increased imbibition of water are the 

 principal factors leading to the formation of probably most of the monsters 

 recorded in these investigations. 



When the egg of Fundidus is subjected to the influence of butyric acid or 

 acetone solutions its membrane is rendered more permeable than it is in its 

 normal environment. On subsequent transfer to pure sea-water the eggs seem 

 to imbibe more water than normally developing eggs, since a temporary 

 increase in the volume of eggs transferred from these acid solutions to pure sea- 

 water can be observed without difficulty. This rapid osmotic imbibition in 

 turn causes a fragmentation of the germinal substance. Some parts of the 

 latter may thus be entirely destroyed, owing to the increase in osmotic pres- 

 sure, while the remainder may go on developing and eventually give rise to 

 various monstrosities. This would account for the formation of meroplasts, 

 recorded in these experiments in very great numbers, the most striking of 

 which are the "solitary eye" and the "isolated eye," i. e., eggs in which an eye 

 develops from a small fragment of the medullary plate, an embryo being either 

 entirely absent or, if present, being in no connection whatsoever with the eye, 

 which has developed independently at a great distance from it. Of these cases 

 of independent development of the eye a relatively great number have occurred 

 in this summer's experiments. 



To blastolytic action caused by an increase in the osmotic pressure of the 

 environment are evidently due also other cases of malformation, such as 



^Werber, E. I., Experimental studies aiming at the control of defective and monstrous devel- 

 opment. A survey of recorded monstrosities, with special attention to the ophthalmic defects. 

 Anat. Record, vol. 9, No. 7. 1915. 



