RADIATION STANDARDS, INCLUDING FALLOUT 343 sion, Division of Biology and Medicine, is now supporting an experimental genetic study of mutation in irradiated pigs, but as may well be imagined, progress is slow and the expenseis high. We need direct evidence of the production of mutations in humans, and of the quantitative level at which mutations are produced in relation to dosage. Indirectly, we may be able to get at this. By growing humancells in artificial culture media and exposing them to ionizing radiation, a number of workers (Puck, Bender, Dubinin, et al.) have demonstrated that the chromosomes are fractured and rejoined in various ways, and that the number of chromosome breaks is linearly proportional to the dose. This has been demonstrated over a range from 10 roentgens up to several hundred rotentgens. Moreover, the number of breaks produced by a given dose in human cells may be compared with the number produced by the same dose in comparabletissue cells of a monkey, mouse, or hamster. Bender has recently reported the results of irradiating with X-rays white blood cells freshly drawn from the human body, and then culturing them long enough to determine the frequency of chromosome breaks in these cells. A linear proportionality between frequency of breaks and radiation dose is demonstrated. In my own laboratory we have used the corneal epithelium as the chosen tissue for such experiments, since in this case it is easy to irradiate the cornea in the living animal and also to irradiate the corneal cells growing in a cell culture, and then to determine whether there is any difference in response as the result of growing thecells outside the body. In preliminary results obtained with the Chinese hamster, a strictly linear proportionality between frequency of chromosome breakage and X-ray dose has been demonstrated when the cornea was irradiated in its normal situation, for a range of doses from 25 roentgens up to 150 roentgens. 'There are thus excellent prospects that in a few years we may have definite quantitative knowledge about the relation of chromosome breakage to dose for a variety of human tissues. So far, no one has succeeded in culturing human reproductive cells, or even pieces of the ovaries or testes, for a sufficient period. Yet it may be hoped that studies on the relationship of chromosome breakage to dose of radiation can eventually be carried out successfully for the reproductive tissues, too. Cells in which chromosomes are broken by radiation nearly always die. Consequently, such damage in a proliferating tissue (one in which the cells are dividing and in which the dying cell can be replaced by new sound ones) is not serious at low doses of radiation. The genetic damage that is serious is what is transmissible to cells that can continue to live and function and, if reproductive celis, participate in the production of offspring that will carry the mutated gene. Submicroscopie lesions in the chromosomes, our so-called point mutations, may also eventually be studied in cells growing in culture. What is necessary is to find a mutation that will produce some kind of chemical or structural alteration which can be observed in the individual cell, or to find some way of killing off the unmutated cells in the culture so as to leave only the mutated ones. Studies such as these are being pursued in a number of laboratories, including my own, and maybe success is around the corner for someone in this elusive pursuit. Even since the 1960 report of the NAS Committee on the Genetic Effects of Atomic Radiation a quite new aspect of the problem has come into prominence. In 1959 it was discovered, in France and Great Britain, that most cases of mongoloid idiocy are attributable to the presence in the cells of an extra chromosome, a very small one (No. 21 according to size) among the 28 pairs of human chromosomes. Shortly afterward two forms of sexual maldevelopment, accompanied by sterility, were discovered to arise, the one from the presence of an extra sex chromosome, the other from the lack of a sex chromosome normally present. Ever since 1915 abnormalities of this same kind had been knownin fruit flies and had been found to be increased in frequency by radiation. They had also been described more recently in connection with certain abnormal types in mice. These errors of chromosome number, which might be called a sort of mutation, arise in two general ways. The commonest is probably what is called non- disjunction, that is, the failure of two matched chromosomes to separate from each other and go singly into the reproductive cells. The result would be forma- tion of one reproductive cell with an extra chromosome and another with one chromosome too few. The other way in which such errors arise is through the loss of a chromosome from the fertilized egg. Recent studies at the Oak Ridge National Laboratory by Liane B. Russell and C. L. Saylors show that when a male mouse is irradiated, it is usually this second sort of error that occurs, 100 roentgens yielding 5.2 percent of cases of loss of the sex chromosome from the ORR: SENS aesbeggSSBaMEREDteppei ahed SSUES ASSESCaSEAREE