This is a personal account of why the author chose to focus on devisin
g techniques for micromanipulating the blastocyst stage conceptus as a
way of investigating early development in mammals. Its aim is to prov
ide insight into what such technical innovations entailed and how they
have contributed to present understanding of both embryology and the
analysis of gene function in mammals. The ability to dissect and recon
stitute mouse blastocysts, and to inject cells or tissue into them, en
abled genes to be harnessed as markers for elucidating the lineage of
cells and interactions between tissues from the stage when differentia
tion is first evident. Most importantly, it made it possible to apply
clonal analysis to the study of cell fate in mammals. The scope of bla
stocyst micromanipulation was further enhanced when embryonal carcinom
a (EC) cells and, particularly, embryonic stem (ES) cells were found t
o be able to participate in normal development and contribute to the g
erm line following injection into the blastocyst. BioEssays 20. 168-18
0, 1998. (C) 1998 John Wiley & Sons, Inc.