Irrepressible: An Interview with Mark Ptashne

While winter storms crippled almost every state fromWisconsin to Florida, our own force of nature blew into California in January in the compact human form of Mark Ptashne (Fig 1). Mark, who holds the Ludwig Chair of Molecular Biology at Sloan-Kettering in New York, had arrived to give a series of seminars on the West Coast. And if that weren’t enough, he also came prepared for a soirée, with his violin in tow. In the late 1960s, while still a Junior Fellow at Harvard, Ptashne became known for the isolation of a specific protein—the bacteriophage λ repressor—and the demonstration that it could bind to specific sequences of double-stranded DNA called operators. This experiment, together with the isolation of the lac repressor by his colleague Walter Gilbert, made manifest the holy grail of that time: François Jacob and Jacques Monod’s elusive repressors, predicted by genetic evidence but working through unknown mechanisms. Over the ensuing decades, Ptashne and his laboratory not only clarified gene regulation in molecular detail in λ, they extended these profound discoveries from bacteria to eukaryotes, making it possible to think about development and evolution rationally, in molecular terms. With his sturdy keel and breakneck speed, the strong wake of Ptashne’s scientific career is impressive. One colleague, quoted in a New York Times article, commented, “Everything we know about gene transcription has come from...Ptashne.” Ptashne is highly regarded for his clarity of thought, as epitomized by his book A Genetic Switch and another, Genes and Signals, co-authored by Alexander Gann. His laboratory’s recent work on gene regulation in eukaryotes, including analysis of sequence specificity and occupancy of nucleosomes, has led to his commentaries on the misplaced efforts of much current epigenetic research. I had been pestering Mark to do a PLOS Genetics interview, and for some time he managed to wriggle out of it. But late on a Saturday afternoon, I was summoned to the home of Sandy Johnson, Mark’s former thesis student and, as it happens, my former husband. Mark was ready to chat, and asked, by the way, could I please bring some Epsom salts so he could soak his hand before the concert. Johnson was called on occasionally to interpret, clarify, and generally calm things down at several points in the interview. When the dust settled, I was left with a transcript of a spirited but highly disjointed conversation that, when redacted, went something like this: Gitschier: I want to talk to you about your upbringing and then I want to talk to you about the big repressor time period of your life. Let’s just start at the beginning. What city were you born in? Ptashne: Chicago, Illinois. Gitschier:Now, your parents. What were their names? Ptashne: Fred and Millie. Gitschier:OK, and what were their professions? Ptashne:Well, my father was a businessman of sorts. When I was about ten, we moved to Minneapolis so he could be in my uncle’s snowsuit business.