When recombination was observed in bacteria, Lederberg re-evoked the old idea of copy-choice that Belling (1928) and Freese (1957) had suggested, proposing that it could also be extended to eukaryotic chromosomes in order to overcome abnormalities such as gene conversion (see Chapter 6): If daughter chromatids were formed by conservative replication, then a copy-choice mechanism might switch synthesis from one chromatid to another, and if the synthesis of the two daughter chromatids from each parental chromosome was not quite synchronized, both might be copied over a short interval from the same parent, thereby giving rise to a 3:1 ratio at a heterozygous site. Replicas can switch from copying off one chromosome to copying off the other repeatedly in short regions of effective pairing, and the switching need not be reciprocal, resulting in both gene conversion and negative interference (Holliday, 1964; Whitehouse, 1965, 317). However, as noted earlier (Chapter 5), there were serious experimental inconsistencies with any copy-choice model of eukaryotic chromosome replication: The model predicted recombination between only the two replicated daughter chromatids, ignoring the fact that all possible pairs of the four chromatids may be involved in crossing-over events; chromosome replication occurred at the S-phase of the cell cycle, prior to meiosis and to its chromosome pairing (Swift, 1950); and this replication of the DNA was semi-conservative (Taylor, 1959).