Just toothpicks and logic: how some labs succeed at solving complex problems.

Abstract

When I was asked to write a biographical piece about Jon Beckwith, it was difficult to know exactly what to do. The details of Jon's career as a scientist are certainly of interest, and many people would be happy to either read or contribute testimonials to Jon's creativity and talent as a mentor. However, it seemed that this could instead be an opportunity to ask if there were any general principles that underlie the continuous success that the Beckwith lab has had in understanding complex problems, such as regulation of gene expression, membrane protein structure, protein secretion, cell division, and disulfide bond formation. Two themes may account for much of this consistency over time and over subject matter: the first is that there are several aspects of how problems are viewed and analyzed in what may be termed the “Beckwith style,” and the second is related to the experimental tools of the bacterial geneticist and in particular the lac operon. These principles can be clearly seen from some early work on the genetics of lac regulation and the mechanism of conjugation as well as initial work on protein secretion in bacteria. While some details of Jon's biography are relevant for this discussion, I refer readers to Jon's recent autobiography for an in-depth view of his experiences, particularly in the area of social and political activity, which are not covered here (3). Jon has been at the Department of Microbiology and Molecular Genetics at Harvard Medical School since 1965, when he was appointed an Assistant Professor (for a recent photograph, see Fig. ​Fig.1).1). Prior to coming to Harvard, Jon had several postdoctoral experiences that undoubtedly contributed to the development of the Beckwith style and the adoption of the lac operon as a powerful tool. FIG. 1. Recent photograph of Jon Beckwith.