Studies are now being done at Oak Ridge National Laboratory on the misincorporation of isoleucine into hemoglobins of experimental mammals in attempts to understand the basis for the elevated isoleucine content in the hemoglobin of some Marshallese. The natural frequency of misincorporation of isoleucine in hemoglobins of marmoset, sheep, and cow and in the alpha and beta chains of pig and rabbit, respectively, is between 2.2 and §.0x107> (69). In irradiated animals the misincorporation appears to be due primarily to translational errors rather than to somatic mutations; in humans it probably represents a combination of translational errors and somatic mutations. 3. Detection of Mutant Proteins* As the least biased approach currently available to an estimation of the potential genetic effects of the exposures sustained by the Marshallese, a series of proteins of the blood serum and erythrocytes have been examined by electrophoresis (34) for genetic variants, in samples derived from children born to persons exposed on Rongelap, Ailingnae, and Utirik and from children born to parents sustaining no unusual radiation exposure. The proteins are as follows: adenosine deaminase, adenylate kinase, aldolase, carbonic anhydrase, 2,3-diphosphoglyceromutase, galactose~l-phosphate uridylyltransferase, indophenol "oxidase," isocitrate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, peptidase A, peptidase B, phosphoglucomutase-1l, phosphoglucomutase-2, 6-phosphogluconate dehydrogenase, phosphoglycerate kinase, phosphohexose isomerase, triosephosphate isomerase, albumin, ceruloplasmin, haptoglobin, hemoglobin A, hemoglobin Aj, and transferrin. The theory is that some portion of the total mutational spectrum will manifest itself in these children as variant proteins present in the child but not in either parent. Further, one would expect a higher frequency of mutational events in the children of exposed than of non-exposed parents. On the other hand, it was realized from the first that the number of children avail- able for study was very small indeed, and it was almost inconceivable that a genetic effect of the irradiation experience could be detected. The control children are of two types: those born to unexposed parents, and those born to exposed parents before the irradiation. In the control population we have tested 1897 gene products for the occurrence of mutation, with no positive findings. In the children born to exposed subjects, we have tested 1835 gene products, again with no mutations. Present knowledge about the frequency of both spontaneous and radiation-induced mutations detectable by electrophoresis in humans indicates that no single population, even the survivors in Hiroshima and Nagasaki, is of sufficient size to answer some of the questions concerning radiation effects. It will probably be necessary to pool the results of studies on a number of different types of populations in order to advance the question materially; the observations on the Marshallese are thus part of a larger body of data which is slowly accumulating. *Drs. J.V. Neel, H. Mohrenweiser, and R.E. Ferrel (U. of Michigan, Ann Arbor). - 35 -