With the passing of Paul Doty on Dec. 5 at the age of 91, the science of biological macromolecules lost one of its great pioneers. Even as he coordinated the research activities of his large laboratory of graduate students, postdoctoral fellows and visiting scientists, Doty managed to focus on his other passion, the bringing together of scientists from both sides of the Iron Curtain to assure that atomic war would not occur.
Paul Mead Doty was born June 1, 1920, in Charleston, W.V. His interest in molecular and physical sciences developed early, and after completing his undergraduate studies at Penn State College (now University) in 1941, he went on to study chemical physics at Columbia University, where he ostensibly undertook his doctorate work under Joseph E. Mayer but in fact worked on the isolation of uranium for the Manhattan Project.
It was during this period that he developed a strong friendship with classmate Bruno Zimm, which led them jointly to accept positions in 1943 under the noted polymer chemist Herman Mark at what was then the Polytechnic Institute of Brooklyn. Out of their three-year scientific partnership emerged the important method of light scattering for the determination of molecular weight and asymmetry of macromolecules based upon earlier theoretical formulations derived by Peter Debye.
With Zimm focusing on the mathematical theory and Doty on the instrumentation and experimental methodology, they characterized the size and shape of a variety of synthetic polymers in papers that are still viewed as classics of polymer chemistry (1). In 1946, Doty went to Cambridge University for a year as a Rockefeller research fellow; then he joined the chemistry department at the University of Notre Dame and a year later the chemistry department at Harvard University, where he remained for the rest of his career. After two decades at Harvard, Doty founded the department of biochemistry and molecular biology.
It was after discussions with Max Perutz during his time in Cambridge that Doty made the critical decision to apply his unique knowledge of polymer science to the investigation of biological macromolecules. Doty went on to confirm that the polypeptides that Perutz had shown by X-ray diffraction of their fibers to be -helices did exist in solution as well in the form of stiff, short-chain molecules of the same size and shape (2). At the same time, he undertook light-scattering investigations of carefully prepared DNA and shocked the Protein/Nucleic Acid Gordon Conference of 1950 by reporting that these nucleic acid molecules had molecular weights of many million and a stiffness sufficiently great that they could not possibly be single chains but rather had to be multistranded (3).
With this beginning, the Doty laboratory went on to a variety of important investigations in the protein field. These resulted in significant contributions to our understanding of the solution conditions that determine polypeptide conformation and to the development of techniques, particularly optical rotatory dispersion, for determining the -helical and β-sheet contents of various key proteins (4) (most notably myoglobin, the helical content of which was confirmed by John Kendrew’s X-ray structure analysis) as well as the helical nature of the three-stranded protein collagen. And with nucleic acids, he investigated the effects of pH and especially temperature on the native properties of DNA, initiating the technique of thermal melting analysis of nucleic acid molecules and thereby contributing to an understanding of their thermodynamics and the conformational differences between duplex DNA and single-stranded RNA (5, 6).