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).
With investigations of the conformational properties and interaction stoichiometry of polyribonucleotides of simple and complex sequence (7) and the separation of the complementary strands of DNA and then their renaturation to biologically active duplexes (8), the groundwork was laid for the complementary strand annealing that proved so critical in making gene cloning possible. In addition, the laboratory’s decisive work on RNA provided the algorithm for RNA secondary structure (9) that today remains the basis for correlating RNA sequences with secondary structure prediction. This work was quickly followed by evidence intimating the existence of a class of RNA in ribosomes that hybridized uniquely to genomic DNA of the same species, but not to that of foreign species (10), what later came to be known as mRNA.
Although Doty continued to guide the scientific activities of his laboratory, he began in the late 1950s to do so at a distance because of his increasing concern with atomic disarmament issues. This new involvement, which began in 1957 when he served as chairman of the Federation of American Scientists, increased as he became more concerned about what atomic war could mean for the world. This concern led him to play a significant role in the creation of the Pugwash conferences and in other contacts with Russian scientists, sometimes at a personal level and at other times in back-channel negotiations at the behest of the U.S. government.
It was these interests as well that led Doty to take on a leadership role in the founding of the Belfer Center for Science and International Affairs, which later became a part of the John F. Kennedy School of Government at Harvard, where he influenced the training of many scientists who now hold important positions in government or academia.
Doty was a leader and a mentor to many. He was exceptionally articulate, wrote beautifully, always directed his focus on major questions and stressed the important. He was careful about experimental detail, accuracy and intellectual honesty, but he was in no way a data collector. He set a very high standard for the work done in his laboratory, inspired others and called for one’s best. He rarely made an effort to teach, yet he taught by example. Ambitious as he was, he recognized the value of permitting the most talented and creative of his associates to function on their own; for such individuals, he had done enough to set the general goals, and he made them feel that there was freedom of operation in the Doty laboratory.
For most of his career, Doty was married to Helga Boedtker, his former graduate student, who did much to manage the laboratory during his nonscientific distractions. She predeceased him 10 years ago. He is survived by a son, Gordon, from his first marriage to the late Margaretta Gravatt, and three daughters with Helga: Marcia, Rebecca and Katherine.
Paul Doty maintained strong friendships with many who were associated with him. He will be sorely missed.
- 1. Doty, P. M., Zimm, B. H., and Mark, H. (1944) Some light scattering experiments with high polymer solutions. J. Chem. Phys. 12, 144 – 145; (1945) An investigation of the determination of molecular weights of high polymers by light scattering. J. Chem. Phys. 13, 159 – 166.
- 2. Doty, P., Holtzer, A. M., Bradbury, J. H., and Blout, E. R. (1954) Polypeptides. II. The configuration of polymers of γ-benzyl-L-glutamate in solution. J. Am. Chem. Soc. 76, 4493 – 4494.
- 3. Doty, P. and Bunce, B. H. (1952) The molecular weight and shape of desoxypentose nucleic acid. J. Am. Chem. Soc. 74, 5029 – 5034.
- 4. Yang, J. T. and P. Doty (1957) The optical rotatory dispersion of polypeptides and proteins in relation to configuration. J. Am. Chem. Soc. 79, 761 – 775.
- 5. Rice, S. A. and Doty, P. (1957) The thermal denaturation of deoxyribose nucleic acid. J. Am. Chem. Soc. 79, 3937 – 3947.
- 6. Doty, P., Boedtker, H., Fresco, J. R., Haselkorn, R., and Litt, M. (1959) Secondary structure in ribonucleic acids. Proc. Natl. Acad. Sci. USA, 45, 482 – 499.
- 7. Fresco, J.R., and Alberts, B. M. (1960) The accommodation of noncomplementary bases in helical polyribonucleotides and deoxyribonucleic acids. Proc. Natl. Acad. Sci. USA, 46, 311 – 321.
- 8. Doty, P., Marmur, J., Eigner, J. and Schildkraut, C. (1960) Strand separation and specific recombination in deoxyribonucleic acids: physical chemical studies. Proc. Natl. Acad. Sci. USA, 46, 461 – 476.
- 9. Fresco, J.R., Alberts, B.M., and Doty, P. (1960) Some molecular details of the secondary structure of ribonucleic acid. Nature, 188, 98 – 101.
- 10. Schildkraut, C., Marmur, J., Fresco, J. R., and Doty, P. (1961) Formation and properties of polyribonucleotide-polydeoxyribonucleotide helical complexes. J. Biol. Chem., 236, PC 2 – 4.
Jacques R. Fresco (firstname.lastname@example.org) is a professor in the department of molecular biology at Princeton University.