Tribute to Paul F. Torrence, a brilliant chemist switching from polynucleotides to nucleosides, oligonucleotides, and back to nucleosides

Dr. Bernhard Witkop, I generated the interest of Dr. Paul F. Torrence to evaluate the requirements of synthetic polynucleotides to induce interferon. His interest, akin to mine, then shifted to 5-substituted 2'-deoxyuridines, which we first evaluated for their activity against herpes simplex virus (HSV) replication and later as tumor cell inhibitors targeted at thymidylate synthetase. The major interest of Dr. Torrence then shifted to the 2'-5'-oligoadenylate (2-5A), which, concomitantly with its target enzyme, RNase L, effected marked antiviral activity, that is, against respiratory syncytial virus (RSV). As the hope(s) for an effective 2-5A therapeutic for RSV or any other virus infection was not realized, Paul Torrence returned to nucleoside analogues, now targeted at poxviruses.