Mutation studies with human fibroblasts.

My attitude toward studying mutation in human fibroblasts at this time is related to that expressed by Dylan Thomas in a note to his "Collected Poems" (1): "I read somewhere of a shepherd who, when asked why he made, from within fairy rings, ritual observances to the moon to protect his flocks, replied: 'I'd be a damn fool if I didn't!' These poems, with all their crudities, doubts, and confusions, are written for the love of man and in praise of God, and I'd be a damn fool if they weren't." The experimental study of mutation in diploid human cells is in its infancy and is still prey to crudities, doubts and confusion in comparison to some submammalian mutation detection systems that are technically neat and genetically characterized. It is generally assumed that, ultimately, we will want to use human cells for mutagenesis detection, but that this will not be possible for some time to come because of their technical limitations. I will submit two propositions for your consideration: (1) technical limitations in using diploid human cells are far from decisive and several opportunities for detailed mutation studies are now available; (2) presented with opportunities for making these studies, "I'd be a damn fool if I didn't!" My plan in this presentation is to summarize with little documentation some ongoing studies of hereditary variation in cultured human fibroblasts. Many of the details are available in papers that are published (2, 3) or submitted for publication (4). I