Geneva Biomedical Research Institute

In 1980 Mark Ptashne published a review entitled How λ repressor and Cro work followed by another, in 1988, called How eukaryotic transcriptional activators work. The bold — almost, some might feel, naïve — ambition these titles betray is unashamedly the author’s: to generate a coherent picture of how genes are switched on and off. Mark Ptashne’s approach has always been transparent. During group meetings he often responded to some piece of data or other by saying that it was fine, but that if one wanted to learn the truth, one had to do the right experiment, and that one couldn’t know what that was unless one had a very clear idea to test of how one thought the world worked. Or he might recall Emerson: “our job is to turn fact into truth.” Few pursue this approach as rigorously as Ptashne — and even fewer as successfully. But then he seeks to understand his golf swing in much the same way: models are built, tested, adhered to, or discarded. Indeed, nowadays he rarely indulges in an actual game, seeing that as an over-elaboration, a murkying of the waters in his quest to understand how his golf swing — and hence, in principle, golf itself — works. Although Ptashne respects those who can move from one scientific problem to another, he himself is driven by an unrelenting passion to understand with complete clarity a single problem. This pursuit has provided us with the conceptual framework in which we understand how proteins bind to specific sites on DNA and effect transcription of nearby genes. Last September, he was awarded The Lasker Prize (see http://www.laskerfoundation.com) for this contribution, which began more than 30 years ago with the isolation of the bacteriophage λ repressor. As an undergraduate at Reed College, Oregon, Ptashne read the classic Jacob and Monod paper on the lac operon and was at once mesmerized by thoughts of finding a repressor. But when he arrived at Harvard in 1961, Matt Meselson and Jim Watson persuaded him that before he could go after a repressor he should attempt something a little