The Effect on the Offspring of Intoxicating the Male Parent and the Transmission of the Defects to Subsequent Generations

Abstract

Three years ago a series of experiments were begun with guinea-pigs in order to test the possibility of modifying the type of development in mammals, so as to produce definite monstrosities, as had been accomplished with lower vertebrates. This primary object has not been fully attained at the present time, yet the experiments have demonstrated several points concerning injury of the germ cells, and have shown that an alcoholized male guinea-pig almost invariably begets defective offspring even when mated with a vigorous normal female. A method has been devised for administering the alcohol by inhalation. The animals inhale the fumes of 95 per cent. alcohol which are readily taken into the pulmonary circulation, and very soon cause a state of intoxication. By this method the stomach is not injured and the general metabolism of the animal is maintained in a healthy condition. Few changes are produced in the tissues of the animals, even after a treatment given six times per week has extended over almost three years. Yet the actual effects Upon the reproductive glands are indicated by the inferior quality of the offspring to which the alcoholized individuals give rise. The animals have been mated in various combinations. First, alcoholized males are paired with normal females, the paternal test, and also the crucial test of the influence of the treatment on the germ cells. Fifty-nine such matings have reached term. Twenty-five of these gave negative results or early abortions. Thirty-four of the fiftynine matings resulted in conception which ran the full term. Eight, or about 24 per cent., of these were stillborn litters containing in all 15 dead individuals. Many of them were somewhat premature. Twenty six, or only 44 per cent., of the matings produced litters of living young, containing a total of 54. Twenty-one, or almost 40 per cent., of these young animals died within a few days or less than four weeks after birth and only 33 of them survived. Many of the 33 survivors are small excitable animals and though not treated themselves have usually given rise to defective offspring in the several cases where they have been mated with one another. The Second combination is between aleoholized females and normal males, the results of which are interesting in comparison with the above. In this combination there are two chances to injure the offspring; in the first place it may arise from a defective egg cell, or secondly, it may be injured by an abnormal developmental environment within the body of the alcoholized female. Fifteen such matings have been made. Three of these, or 20 per cent., gave negative results, or were possibly aborted very early. Three stillborn litters of nine individuals were produced. Sixty per cent. of the matings gave living litters, as against 44 per cent. in the first combination between treated males and normal females. The proportion of surviving young is, however, less from the treated females than from the treated males. Of 19 living young, 9 died soon after birth and 10 survived. The third combination was between alcoholized males and females. Twenty-nine such matings gave in 15, or more than 50 per cent., of the cases negative results or early abortions. Three stillborn litters occurred, each consisting of two individuals. Only 11 living litters were produced containing 16 young, 9 of which survived while 7 died soon after birth. All of the matings of the treated animals may be combined and compared with control matings as follows- In a total of 103 full term matings, 43, or almost 42 per cent., have given negative results or early abortions, while 35 control matings failed in only two cases, or about 6 per cent., to yield a full term litter. Fourteen, or 131/2 per cent., of the matings gave stillborn litters consisting of 30 dead individuals. Only one stillborn litter occurred in the 35 control matings; this was a large litter of 4 individuals and the mother seemed almost unable to carry them. The 103 matings gave only 46 living litters, about 45 per cent., while 32 living litters, or 911/2 per cent., were produced by the 35 control matings. The 46 living litters from the alcoholic matings contained 89 young, 37 of which died shortly after birth and 52 survived. The 32 living litters from the normal animals consisted of 60 individuals only 4 of which died while 56, or 93 per cent., of them survived. Of 119 full term young, living and stillborn litters, produced by the alcoholic animals only 52, or less than 44: per cent., survived as against the 56, or 871/2 per cent., survivors among the 64 full term control offspring. The offspring derived from the alcoholic individuals are termed second generation animals and were not themselves treated with alcohol. In three cases second generation individuals have been mated with normal and have given perfect results, although the litters have been small. It might seem as though the normal mate possessed a strong tendency to counteract any defect which may have been present in the second generation animal. Mating second generation individuals with alcoholized guinea-pigs gave very different results. Two out of three such matings produced stillborn young, one of which was grossly deformed. The third mating gave two surviving young. Nineteen matings have been made between second generation animals, the outcome of which compares very unfavorably with that from the control matings, while the data are closely similar to those obtained from the alcoholic matings. Seven, or almost 37 per cent., of the matings gave negative results. Twelve living litters were born consisting of 19 individuals, 6, or about 32 per cent., of which died very soon after birth and showed various nervous disorders; one was entirely eyeless and decidedly deformed. From the number of records available one might conclude that the effects of the alcoholic treatment were as pronounced upon the offspring of the second generation animals, although they had not been directly treated, as upon the offspring of alcoholized individuals. The poison injures the cells and tissues of the body, the germ cells as well as other cells, and the offspring derived form the weakened or affected germ cells have all of the cells of their bodies defective, both soma and germ, since each of the cells is a descendant of the injured germ cell combination. In this manner the defects or degenerate conditions are transmitted or passed to subsequent generations.