Lessons learned from an unstable genomic landscape.

PURPOSE This brief historical perspective will highlight the many accomplishments of the late William 'Bill' Morgan, and how his laboratory during the mid-1990s shaped the field of genomic instability. Bill focused on the processes responsible for radiation-induced genomic instability, and while ionizing radiation was known to induce this phenomenon, the precise causes were poorly understood. Here we revisit Bill's unique approach to these problems, as he advocated the use of novel mammalian cell lines to tease apart the mechanisms responsible for destabilizing an otherwise stable nuclear genome. CONCLUSIONS Genomic instability is a multifaceted process posited to be the driving force behind multistep carcinogenesis. Bill used a variety of innovative techniques that ultimately refined our understanding of the causes and consequences of radiation-induced chromosomal instability and the role it played in cancer predisposition. The central concepts of genomic instability fit nicely with the mutator phenotype hypothesis proposed by Lawrence Loeb, both of which represent functionally similar frameworks for describing how genomic stability can be compromised. The field of genomic instability has since advanced considerably, and much of our current knowledge is due to the efforts of Bill Morgan.