315. 1995 Hereditary Eye Defects - Howe Jour. A.M.A. June 29, 1914 The plan to attain these four objects is to: 1. Bring the bibliography to date. 2. Arrange it according to diagnoses. 3. Add new family histories of such eye defects. 4. Chart certain histories reported previously only in narrative form. 5. Compare the relation of such defects with the mendelian or other principles of heredity. 6. Show the importance of a differential diagnosis between defects really hereditary and those due to infection (syphilis). 7. Suggest a plan for the prevention of hereditary blindness by sequestration, or by sterilization if the transmitter of the blindness so elects. The reassuring statement should be made at once that it is not intended to cover all of this ground in this paper. For example, the first and second steps in the proposed plan are represented by what may be called Exhibit A. This is a bibliography in the form of a card catalogue. The literature up to 1901 was collected and arranged, according to diagnoses, by Greenouw. That list contained 324 references. Loeb published his bibliography in 1909, but as his list partly duplicated that of Greenouw, and was arranged alphabetically - not according to diagnosis - and as an assistant has found over 200 real or supposed family histories of heredity, it seemed best to make a new list from 1901 and rearrange all according to diagnosis. That constitutes the present list of over 700 titles brought practically to date and arranged on a unified plan. The third step is represented by Exhibit B. This is a group of twenty-four charts of new family histories of hereditary eye defects. These were obtained by examining the files at the Eugenics Record Office of the Carnegie Institution of Washington at Cold Spring Harbor, N.Y., and acknowledgment is here due to the director, Dr. Davenport, for the unusual opportunity this afforded. The fourth step is represented bu Exhibit C. This is a collection of over thirty charts of hereditary eye defects. These histories were published in narrative form, and as such were difficult or almost useless for study or comparison. A few charts already published were also added to show good examples of a defect which is really hereditary and one which is not, and also to show when a defect is "dominant" or "recessive." The importance of this differentiation will appear later. It is possible now only to mention these three exhibits. They will be explained in detail when published. We come then to our fifth step. To state this in slightly technical terms, we ask, does a certain chart suggest in any degree the mendelian law of descent? If so, is the defect dominant or is it recessive? Or does the chart show an example of sex linkage, or are other principles of heredity involved? These are new terms to many of us, but in this paper we have to take for granted a knowledge of the wonderful law discovered by that extraordinary character, the monk, Gregor Johann Mendel, and also what that law means to students of genetics of today. The Mendelian Law An example of mendelian descent, as demonstrated in the eyes of fowls, will recall the more important points: If one fowl having a dark red iris is mated with another that has a gray or pearl colored iris, the descendants in the first generation, called technically the first filial generation, and usually indicated F[inferior]1[end inferior], will show red irises slightly mottled with pearl. That is, it happens that the red iris in poultry "dominates" almost entirely over pearl. But if members of this F[inf]1[end inf] be bred with each other, then in the second filial generation, or F[inf]2[end inf], we find, on counting the offspring, that about one fourth have their irises red, one fourth of them pearl, and half have mottled eyes. If the red "dominates" were complete, then the proportion would be three red eyed to one pearl; but breeding tests would show that, on the average, two thirds of those with red eyes were hybrids. If now, we inbreed those f[inf]2[end inf] individuals, we find when a red-eyed fowl is bred with a corresponding red-eyed fowl, the progeny are all red-eyed, for any number of generations. Also, when the pearl-eyed fowl is bred with a pearl-eyed fowl, the progeny are all pearl eyed for any number of generations. But when two of the intermediate type in F[inf]2[end inf] are inbred, the eyes of their progeny in F[inf]3[end inf] are not all red, but their progeny in F[inf]3[end inf] break up into one red, two mottled and one pearl, as in F[inf]2[end inf]. When these groups in F[inf]3[end inf] are again inbred, we find in the succeeding generation F[inf]4[end inf] the same behavior. The mendelian law is usually stated briefly by letters. Thus, if we denote the dominant parent having the red iris by D, and the recessive parent having the pearl iris by R, the offspring in F[inf]1[end inf] is indicated by D (R ), the R being in parenthesis to show that it is recessive to D. The hybrid D (R ) when inbred gives offspring in F[inf]2[end inf] in the ratio DD + D (R ) + D (R ) + RR. The first DD breeds true. The RR also breeds true. But each of the two intermediate D (R )'s produce in F[inf]3[end inf] a corresponding series of DD + D (R ) + D (R ) + RR. The mendelian law is also illustrated by a diagrammatic arrangement of the letters which indicate the groups of four. As some of the published diagrams seemed to make the sequence entirely clear to me at first, I have outlined the details of Mendel's law as shown in the accompanying diagram. It may also prove of assistance to other students, even if it be rather schematic. Other Principles of Heredity Sex linkage is another principle of heredity to which attention may be called. This is the tendency which certain characteristics have to develop exclusively or predominantly in the male members of the family, especially in certain crosses. For our purposes, however, it must suffice to recall the fact that among the diseases appearing predominantly or exclusively in the male line, at least in certain families, are atrophy of the optic nerve, color blindness, night blindness and probably other defects. [central graphic]