C. C. Little

Differences Between High and Low Breast Tumor Strains of Mice When Ovariectomized at Birth.

Conclusion Marked differences appeared in strains of mice when they were ovariectomized at birth and then examined in later life. The high tumor J AX dba and J AX C3H strains showed stimulated uterus, vagina and mammary glands. The adrenal glands exhibited extensive nodular, hyperplastic areas. All of these organs of the low tumor J AX C57 black strain remained essentially unstimulated. To ascertain whether the above differences are characteristic of all high and low tumor strains, other strains are being studied.

The genetics of cancer in mice.

There are three levels at which genetic studies affect cancer research. These are concerned with the transplantation of tumours, the experimental induction of tumours by carcinogenetic agents, and the ‘spontaneous ’ incidence of tumours which occurs without conscious effort by man. At each of these levels the search for genes as well as for other types of parental influence is instructive. In spite of apparent dissimilarity of opportunity involved in the different areas of experimentation, there are many ways in which results obtained at any one of these levels may contribute to our solution of problems encountered in the other two. Beyond the search for genes, however, there lies another important application of genetic methods to the cancer problem. This is continued inbreeding with the object of reducing genetic variability to a minimum. By this process the morphological and physiological characters which have a genetic basis become uniform and fixed within the strain. Recognition of the need of a broad and interrelated attack on the problem of cancer has been discussed by a Committee on Cancer Research (1938) appointed by the Surgeon-General of the United States and, more recently, by a Committee on Growth appointed in 1945 by the National Research Council. There is also a general discussion of the field of parental influence (Little, 1944), which may help to show the many levels and mechanisms involved in the genetic approach to the cancer problem. It seems best to make the major type of subdivision of this review on the basis of three levels to which reference has been made, namely, transplanted tumours, induced tumours and spontaneous tumours.

The Occurrence of Three Recognized Color Mutations in Mice

To sum up the facts above recorded it may be stated that: 1. A previously recorded mutation of the gray-bellied agouti pattern, known as white-bellied agouti, has arisen in two experiments on color inheritance in mice. 2. In experiment A it has arisen independently three times in a hybrid race of mice. 3. In this experiment there has been no selection in the direction of the mutation. 4. In experiment B it has arisen once in an inbred race in which selection was being carried on. 5. In this race the mutation represents a variation in exactly the opposite direction from that in which the selection was being made. 6. A recessive pink-eyed mutation has occurred in a closely inbred dilute brown race. A similar mutation has appeared in a hybrid race into which one animal from the dilute brown race probably introduced the mutation. 7. A mutation involving loss or suppression of the black producing factor has arisen in a stock of inbred wild mice. This has caused the appearance of brown agouti young. 8. The wild race in which this occurred is related to the hybrid race (see conclusion 2) in which the white-bellied agouti mutation appeared three times. The suggestion is offered that a tendency to germinal instability may have been transmitted by male 131 a common ancestor of both races.

The inheritance of susceptibility to implants of splenic tissue in mice. I: Japanese waltzing mice, albinos, and their F1 generation hybrids

The use of the terms “auto,”“homio,” and“hetero” transplantation has been general and of great value in the long series of experiments which have dealt with the transplantation of normal and of neoplastic tissues in vertebrates. Following a number of experiments in this field, covering a wide range of material, it has become generally recognized by biological investigators that the closer the genetic relationship between the host and the donor of the graft tissue, the greater is the likelihood of persistent and progressive growth of an implant of tissue from one to the other. Similary it has been found that in the ordinary“laboratory” races of mammals, inbreeding has not been intensive enough to have produced a close degree of genetic resemblance between individuals within the race. IVitliout this resemblance the continued growth of tissue transplants made from one animal to another is impossible. When close relatives such as parent and offspring or litter nates are picked for this interchange of implants, there is, as Loeb and others have pointed out, more chance of persistence of the implants than when unrelated animals are used. Loeb 1 has proposed the term“syngenesio-plastic transplantation” for experiments involving the closc relatives referred to. When, however, closely inbred races of known genetic constitution are used, results are obtained Which show that the distinctions between“homio,”“syngenesio,” and “auto” transplantations are only relative and may delibrately broken down by picking animals of certain definite genetic constitutions for experirnentation. Thus in animals of a closely inbred and genetically homogeneous strain of Japanese waltzing mice [already described in connection with experiments on the inheritance of susceptibility to transplanted tumors 2 ], the general reactions of an individual to subcutancous transplants of bit of its own spleen (autotransplants), or to bits of the spleen of another Japarlesc waltzing mouse of the same inbred race (honziotransplanlts) were the same.

The effects of selection on eye and foot abnormalities occurring among the descendants of x-rayed mice.

IN 1921 the writer and Bagg discovered certain abnormalities of the eyes aiid feet in mice. These particular genetic abnormalities have occurred only among the descendants of certain animals which as adults (non-pregnant females ancd males) were treated with light doses of X-rays over the whole body. A series of papers dealing with the various abnormalities from genetic ancd anatomical points of view are included in the bibliography of this note. The object of the preseiit communication is to record the results of selection within the abnormal race as it is at present being carried on. It should be recalled that whereas Bagg has at present aiiimals descended without an outcross from the original abnormials, the mice which provide the primary data incorporated in this note are the result of either oiie or two outcrosses wNNith a normal albino race followed by close (brother to sister) inbreeding and, in certain of the lines, selection of the abnormal individuals as parents. The ancestry of most of these

The Incidence of Mammary Cancer in a Cross between Two Strains of Mice

A consideration of the eases in which linkage was observed, i.e., eases in which the difference between the means of the recessive and dominant members of the factor pairs was as great as or greater than four times its probable error, gives the following results: Of course the actual size factors may be responsible for a larger portion of the variance if not completely linked with the qualitative gene. The above computations indicate that the size genes definitely located account for a distinct, although perhaps rather minor, portion of the variance in the respective size characters. It further appears probable that the latter are influenced as well by several or many genes situated in a number of chromosomes. C. V. GREEN ROSCOE B. JACKSON MEMORIAL LABORATORY, BAR HARBOR, MAINE

Note on the occurrence of a probable sex-linked lethal factor in mammals.

environment and the behavior of the macronueleus and that the macronucleus assumes different shapes and appearances under different cultural conditions. Is this amicronucleate paramecium able to exist indefinitely without conjugation involving a micronucleus and without reorganization of nuclear material, or is there another type of reorganization in this race? A nuclear reorganization, if present, must evidently be of a different ype from that described by Erdmann and Woodruff. These and similar problems are interesting, not only in themselves, but because ParameciuAm has been studied in great detail by Jennings and others with reference to the occurrence of cytoplasmic variations. The amicronucleate race, however, is important because the variation is one of nuclear structure. The importance and interest of the study is increased by the fact that the micronucleus is usually considered to be an aggregation of generative or hereditary chromatin and the body which supposedly initiates reproductive processes of all types and from which, in sexual reproduction, the new nuclei are formed. EUGENE M. LANDIS ZOOLOGICAL LABORATORY UNIVERSITY OF PENNSYLVANIA

Some factors influencing the human sex ratio.

In 1908 R. and M. De W. Pearl 1 published data derived from the vital statistics of the city of Buenos Ayres, concerning the sex ratio in the following types of matings: (1) Italian × Italian, (2) Spanish × Spanish, (3) Argentine × Argentine, (4) Italian × Argentine , (5) Spanish × Argentine . Of these crosses it will be noted that three are not racial crosses and two are. The data obtained by the Pearls stretched over a period of ten years. Although including very large numbers their data has certain minor disadvantages, for the most part frankly recognized by the authors themselves. First in importance is the fact that their data do not take still births into consideration, and second, the Argentine race may properly be considered as itself somewhat of a mixture and therefore less likely to breed as a pure race. If however the first three crosses be recorded as pure racial matings and the last two as racial hybrids, the ratio of males to 100 females in the two types may be compared as follows: It will be noted that there is a significant excess of males in the hybrids. The Pearls note this fact and state in addition that environmental differences also fail to account for the results. They further agree that experimental investigations are necessary in order to reach adequate explanations for the observed facts. It is believed that a close approximation to experimental conditions exists at the large lying-in hospitals. Here the patients are observed carefully, the sex of every offspring, including still births recorded, and the environmental conditions are for at least the period of confinement, as nearly equal as possible. The nationality of the parents of every child is recorded and the data thus obtained although not including nearly as large a number of cases as that of the Pearls, may, I believe, properly be considered accurate. During the past few months therefore, a study has been made of the records at the Sloane Lying-In Hospital, New York City.

Lipid-steroid fractions of mouse adrenal lipids.

The amount of the lipid material of the mouse adrenal gland was demonstrated by Vicari1 to vary with the strain used. The technic and method applied was histological in nature. This report deals with initial experiments in separating the lipid material of adrenal glands of different strains of mice into 2 fractions.

Some Contributions of the Laboratory Rodents to Our Understanding of Human Biology

IN the halcyon days some thirty years ago when the small group of then existing experimental mammal geneticists was intellectually drunk on the bock beer of newly rediscovered Mendelism, the idea of such a topic as that which I am to discuss would not even have entered the genially bewildered heads of a program committee. It takes the sobering effects of a huge mass of scrambled literature extending over three decades to make biologists begin to consider the possible debt which they, and the generation which they represent, owe to any given type of material. Only after having filled the avid maw of research workers faithfully and well for a long time is the lowly plant or animal given a partnership right to have its name included onl the titular signboard of a general paper in a symposium of this sort. However, to one who still enjoys titillating his long abused and ample nostrils with the more than ebb-tidal aroma of the rodent laboratory, and who still thrills at filling his increasingly carcinophilic lungs with the rat and rabbit-ridden, guinea pig-glutted and mouse-muddled air of that enlivening environment, the challenge of presenting such a paper is ~a welcome one. It is amazing how effectively experimental work with laboratory rodents has shaped the development of our whole concept of human biology. The influence of the comparative point of view has nowhere been more consistent and important in providing 1 Read at a Symposium of the American Society of Naturalists ill joint session with the American Society of Zoologists, the Botanical Society of America and Section H. The American Association for the Advancement of Science, Richmond, Virginia, December 30, 1938.