While such early biochemical techniques found grudging acceptance in the biology community, for the most part they did not impact the main theoretical problems of evolution and population genetics. This would change as molecular biology shed more light on the physical and chemical nature of genes. At the time that molecular biology was coming into its own in the 1950s, there was a long-running debate—the classical/balance controversy—over the causes of heterosis, the increase in fitness observed when inbred lines are outcrossed. In 1950, James F. Crow offered two different explanations (later dubbed the "classical" and "balance" positions) based on the paradox first articulated by J. B. S. Haldane in 1937: the effect of deleterious mutations on the average fitness of a population depends only on the rate of mutations (not the degree of harm caused by each mutation) because more-harmful mutations are eliminated more quickly by natural selection, while less-harmful mutations remain in the population longer. Muller dubbed this "genetic load". Muller, motivated by his concern about the effects of radiation on human populations, argued that heterosis is primarily the result of deleterious homozygous recessive alleles, the effects of which are masked when separate lines are crossed—this was the "dominance hypothesis", part of what Dobzhansky labeled the "classical position". Thus, ionizing radiation and the resulting mutations produce considerable genetic load even if death or disease does not occur in the exposed generation, and in the absence of mutation natural selection will gradually increase the level of homozygosity. Bruce Wallace, working with J. C. King, used the "overdominance hypothesis" to develop the "balance position", which left a larger place for overdominance (where the heterozygous state of a gene is more fit than the homozygous states). In that case, heterosis is simply the result of the increased expression of heterozygote advantage. If overdominant loci are common, then a high level of heterozygosity would result from natural selection, and mutation-inducing radiation may in fact facilitate an increase in fitness due to overdominance. (This was also the view of Dobzhansky.) Debate continued through 1950s, gradually becoming a central focus of population genetics. A 1958 study of "Drosophila" by Wallace suggested that radiation-induced mutations "increased" the viability of previously homozygous flies, providing evidence for heterozygote advantage and the balance position; Wallace estimated that 50% of loci in natural "Drosophila" populations were heterozygous.