In 1979 teams at Harvard and Caltech extended the basic idea of making DNA copies of mRNAs in vitro to amplifying a library of such in bacterial plasmids. In 1982–1983,  the idea of selecting random or semi-random clones from such a cDNA library for sequencing was explored by Greg Sutcliffe and coworkers. and Putney  et al. who sequenced 178  clones from a rabbit muscle cDNA  library. In 1991 Adams and co-workers coined the term expressed sequence tag (EST) and initiated more systematic sequencing of cDNAs  as a project (starting with 600 brain cDNAs). The identification of ESTs proceeded rapidly, millions of ESTs now available in public databases (e.g. GenBank).
In 1995, the idea of reducing the tag length from 100 to 800 bp down to tag length of 10 to 22 bp helped reduce the cost of mRNA surveys. In this year, the original SAGE protocol was published by Victor Velculescu at the Oncology Center of Johns Hopkins University. Although SAGE was originally conceived for use in cancer studies, it has been successfully used to describe the transcriptome of other diseases and in a wide variety of organisms.