William Ernest Castle

“ The grouping of the young in a series of generations is only approximately accurate, for practical considerations have often led us to mate together animals which belonged to different generations of offspring. When, for example, an animal of generation 2 was mated with one of generation 4, the question would arise: To what generation do the offspring belong? In deciding this question we simply added one to the mean of the generations to which the respective parents belonged. ”

“ But if the races crossed differ by more than one factor, and if, further, neither parent is homozygous as regards the factors in which they differ, then we may expect an increase in variability both in F1 and in F2. This is exactly what we observe when the minus race is crossed with either the plus race or its derivative, the mutant race.
If we suppose that the plus race and the minus race differ from each other by certain “modifiers,” we can not suppose that the plus and the mutant races differ by these same modifiers. They differ in some other single respect ”

“ The offspring as a group average lower in grade than their parents—that is, their mean regresses on that of the selected parents, but because of the higher mode about which variation occurs in each generation certain of the offspring are of higher grade than their parents. ”

“ Hansford MacCurdy completed, under the direction of the senior author, a study of the inheritance of color in rats. His studies had shown that the piebald pattern of “hooded” rats behaves as a mendelian recessive character in relation to the uniform or nearly uniform coloration of wild rats, but that the hooded pattern, when extracted from a cross with wild stock, shows a different variability, the pigmentation of the extracted recessives being increased in extent. This result was interpreted as showing the unsoundness of the current doctrine of “purity of the gametes” in mendelian crosses. ”

“ The early generations include too few individuals to be of much statistical value, but where the number of offspring rises to 500 or over, the statistical constants acquire undoubted value. The data have been given in the form of correlation tables which will repay careful study. In the tables a single entry has been made for each individual offspring in that row which corresponds with the mean grade of its two parents. Thus, if one parent were of grade 2 and the other of grade 21⁄2, the offspring would be entered in the row 21⁄4 along with the offspring of parents both of grade 21⁄4. ”

“ The upper group in F2 should contain a larger proportion of homozygous mutants than in F1, and since the parents of F3 were chosen from this upper group of F2 offspring, it is not surprising that the 11 F3 offspring recorded up to this time all fall in the upper group. The mean of this upper group is remarkably constant through the three generations, [28] and the variability of the group as measured by its standard deviation is also low, namely, 0.19. This indicates that the mutant character is a strongly dominant unit in relation to the ordinary condition of the plus series. ”

“ If a different one can be found we are quite ready to discard the hypothetical modifiers as a needless complication, contenting ourselves with the supposition that the unit character for hooded pattern is itself variable, and that for this reason racial change in either plus or minus directions may be secured at will through repeated selection. ”

“ As a further test of the permanency of the modification effected by selection in the hooded pattern of rats, crosses have from time to time been made of the selected races with a pure wild stock, i. e., with ordinary wild animals caught in traps. In all cases the wild animals used were known to be homozygous as regards gray coat and self pattern, since when crossed with black-hooded animals they produced only gray self offspring. ”

“ When animals of the plus selection series are crossed with animals of the minus selection series, an F1 generation of offspring is obtained which varies about a mean intermediate between those of the respective uncrossed races. Thus, from an examination of Table 50 it will be seen that when -2 animals of generation 6, minus series, were crossed with +3.50 or +3.75 animals of generation 5, plus series, an F1 generation (Series 1) was obtained consisting of 93 animals of mean grade +0.06. This generation is rather more variable than either uncrossed race, its standard deviation being 0.71. ”

“ When such homozygous conditions are secured, selection will cease to modify the race. The experiment has progressed far enough to show that extensive modification through selection is possible without any marked falling off in variability. No indication is observable that selection will become ineffective before an all-black rat is obtained in the plus series and an all-white rat in the minus series. A nearly all-black race of rats has already been secured. We propose to continue the experiments until demonstrative evidence is obtained. ”

“ But regression may be expected from the character of aberrant parents back toward the normal of the previous generation, yet this regression will in general be less than the departure of the aberrant parents from the normal of their generation. If one desires in such a case to obtain continuous and progressive departure from the normal in either a plus or a minus direction, he need only select continuously in the desired direction. ”

“ If we assume that there exists at the outset a definite number of modifiers and that these possess a definite and unchanging power to modify, then it is evident that selection can do nothing but secure homozygous conditions as regards the presence or absence of these modifiers. ”

“ All perhaps would agree that it implies the existence in the germ-cell of specific determiners essential for the production of particular characteristics in the offspring. Further, no one probably will object to the statement that it implies a dual or duplex condition of the zygote as regards determiners and a simple or simplex condition of the gamete. Thirdly, the fact will be admitted by all that most mendelizing characters are wholly independent of each other in heredity, for which reason we are forced to suppose that their determiners are distinct within the germ-cell. ”

“ The regression from a new and extreme class of parents is at first large, but decreases as the selection is repeated and finally disappears altogether when the average of the race becomes equal to the particular grade under discussion. ”

“ In this genotype theory we are dealing only with a new and more refined aspect of the “theory of pure gametes.” It is not a necessary part of mendelism, not even an original part; but it is very important for us to know whether it is true or not. For if it is true, selection unattended by hybridization is largely a waste of time, as De Vries and Johannsen have maintained, and Jennings and Pearl have reiterated. ”

“ For if the mutant and the plus race are alike as regards the modifiers, but differ only in the main factor, then no change in variability should result from intercrossing them, but only alternative conditions as regards the main factor. ”

“ Will they prove to be more stable than the modifications ordinarily secured by selection in our experiments? To test this matter, we have raised two additional generations of offspring from the two mutants and have bred a second generation of offspring from each of the four groups of F1 offspring recorded in Tables 51 and 52, derived from matings with the plus and minus races respectively. ”

“ It may also be seen from an examination of Table 50 that among the F1 offspring produced by crossing the plus and the minus series there are differences in transmission, as there are in the expression of the hooded pattern. In general those F1 individuals which are of high grade produce offspring of higher grade than do their low-grade brothers and sisters. ”

“ During the academic year 1906-7, the experiments were in immediate charge of Mr. W. G. Vinal; during 1907-8 the plus series was in charge of Mr. H. S. Rand, while the minus series was in charge of Mr. F. C. Bradford. Throughout this time the experiments were closely supervised by the senior author, who assisted in the “grading” of every litter of young. In October 1908 the junior author began his association in the experiments, which has continued up to the present time. ”

“ Top row, a set of arbitrary grades used in the classification of the rats studied.
Middle and bottom rows, skins of rats graded as indicated by the numerals above each skin. The animals graded, +4, +41⁄4 and +43⁄4, being entirely dark above, are shown in ventral view. ”

“ By crosses with such rats the supposed modifiers may become associated with the hooded pattern in extracted recessive individuals and so increase its extent. Such increase does actually occur in experiment. ”

“ In the next case two females of the plus series, belonging to generations 5 and 6, respectively, were crossed with a wild male and their children were bred inter se. There resulted 38 hooded grandchildren, as shown in the next to the last row of Table 42. The range of the grades of these hooded grandchildren was similar to that of the grandchildren in the foregoing case, but their mean was somewhat higher, as [18] we should expect, since they are descended from more highly selected individuals ”