1. Before my time: forerunners of molecular cytogenetics
The first localization of nucleic acids by in situ hybridization to
metaphase chromosomes was described by Pardue and Gall in 1970
[1]. Hybridization of [3H]-labeled mouse satellite DNA and its
complementary RNA were found to localize to the pericentromeric
regions of every chromosome except the Y. I remember reading
about this work while I was in graduate school at the Oregon Health
& Science University, and I realized that in situ hybridization had the
potential to be a truly special and powerful method. I was intrigued
by the ability to query chromosomes and entice them into yielding
their deepest secrets. Everyone wanted to know what DNA
sequences existed in the euchromatic and heterochromatic regions
of specific human chromosomes, and there was keen interest in
determining the map locations of specific genes. However, the
resolution of the radiolabeling method was inherently low and the
technique was cumbersome, with some hybridizations requiring
weeks to obtain enough [3H]-disintegrations to evaluate. To
complicate matters, chromosome banding methods were in their
infancy and it was clear that further technological advances would
be needed before in situ hybridization would see widespread use. I
was occupied with other interests but the field of cytogenetics had