VINOGRAD, JEROME, RUBEN

(b. Milwaukee, Wisconsin, 9 February 1913; d. Pasadena, California, 3 July 1976)

physical biochemistry, molecular biology.

Like many scientists who undertake research in interdisciplinary fields, Jerome Vinograd enjoyed a diverse education. Son of Oscar and Bertha Bernstein Vinograd, he attended the University of Minnesota for two years before leaving in 1931 to study colloid chemistry under Herbert Freundlich at the University of Berlin. After Freundlich emigrated to London in 1933, Vinograd continued his apprenticeship with him at University College for two more years. He then returned to the United States, where in 1937 he obtained an M.A. in organic chemistry unde W.G. Young at the University of California at Los Angeles. The same year he married Sherna Shalett, with whom he had two daughters. Vinograd completed his graduate work at Stanford University, receiving a Ph.D. in physical chemistry in 1940 under J. W. McBain. He remained active all his life, despite major heart attacks in 1954 and 1969. He was elected to the National Academy of Sciences in 1968. Following the dissolution of his first marriage, he wed Dorothy Colodny in 1975.

Vinograd’s early career (1941–1949) was spent as a research chemist for the Shell Development Company in Emeryville, California. As in his work with McBain, this period involved research in colloid chemistry: the behavior of detergents, the structure of micelles, and aspects of catalysis related to petroleum chemistry. Following a year with Shell’s British subsidiary, Vinograd returned to academe in 1951 as a senior research fellow under Linus Pauling at the California Institute of Technology. There he continued his research on colloids, publishing a series of papers on the mechanism of gelation, but increasingly he focused his attention on the structure and properties of biological molecules, especially hemoglobin, myxomyosin, and mocrosomal nucleoprotein. In extending the scope of his research to proteins (and later to nucleic acids), Vinograd employed his training in physical and colloid chemistry to relate properties of viscosity and sedimentation to the molecular structure of biological components.

Vinograd remained on the faculty of Caltech until his death, receiving an appointment as professor of biology and chemistry in 1965 and subsequently being named to the Ethel Wilson Bowles and Robert Bowles chair in 1975. The bulk of his research was concerned with the theory and applications of the ultracentrifuge in biochemical research. In 1957, with Matthew Meselson and Franklin W. Stahl, Vinograd published a seminal paper on “density gradient centrifugation,” in which graditions in the density of a cesium chloride solution subjected to a high centrifugal force could be used to resolve mixtures of components with small differences in molecular weight. This technique provided the first experimental verification of James D. Watson and Francis Crick’s proposal that the process of DNA replication was semiconcervative: Meselson and Stahl used¹⁵N-labeled DNA to show that the sedimentation rate of the daughter DNA duplex required that it contain one polynucleotide stand from the parent molecule. The buoyant density method quickly found widespread application in the characterization of nucleic acids and other macromolecules.

Vinogard continued to seek improved techniques for the ultracentrifuge. In 1959, with Meselson and Eugene Robkin, he developed an optical system for photographing the sedimentation bands in a rotating ultracentrifuge cell. He also introduced in 1963 the technique of “band sedimentation in self-generating density gradients,” in which the material to be sedimented was layered as a thin band on top of the salt medium rather than initially being dispersed within the bulk solution: such an approach required smaller quantities of material and gave better results that the moving-boundary technique he had previously developed.

In addition to advancing separation technology, Vinograd contributed extensively to the understanding of the topological properties of the nucleic acids. In 1963, simultaneously with Renato Dulbecoo and Marguerite Vogt, he and Roger Weil published the first report of closed circular DNA, isolated from the polyoma virus. From the changes in sedimentation rate of viral DNA after it underwent one or more strand scissions, Vinograd subsequently deduced that the DNA must possess a locked-in, twisted structure, that is, the molecule exists as a “superhelix” with extra turns that cause it to be especially compact. In 1966, from a study of the unwinding of the supercoil in the presence of ethidium bromide, which intercalates between the bases, Vinograd formulated a relationship for describing the structure of circular DNA: the “topological winding number” is the sum of the “duplex winding number” and the “superhelix winding number” (α = β + γ). Vinograd continued to focus on the properties and occurrence of circulat DNA until his death. The terminology he developed became the standard nomenclature for describing the topology of nucleic acids.

Vinograd’s career, like that of many pioneers in molecular biology, illustrates the intellectual and geographical migrations that often brought physical scientists into the province of biology. His studies of DNA, begun when he was more forty years old and working in a subordinate position as a research fellow and later as a research associate at Caltech, reveal a senior scientist undertaking a radically different direction in his professional life. Vinograd’s contributions to the technique and theory of nucleic acids bear witness tot he success with of nucleic acids bear witness tot he success with which he applied his physicochemical background to the understanding of biological macromolecules.

BIBLIOGRAPHY

I. Original Works. Vinograd published over one hundred research papers in journals such as Proceedings of the National Academy of Sciences, Journal of Molecular Biology, and Journal of the American Chemical Society. In particular, see “Equilibrium Sedimentation of Macromolecules in Density Gradients,” in Proceedings of the National Academy of Sciences, 43 (1957), 581–588, written with M. Meselson and F. W. Stahl, and “The Cyclic Helix and Cyclic Coil Forms of Polyoma Viral DNA,” ibid., 50 (1963), 730–738, written with R. Weil, An autobiographical summary and a set of selected references are in “Centrifuges, Circles, and Cancer,” in K. J. Mysels, C. M. Samour, and J. H. Hollister, eds., Twenty Years of Colloid and Surface Chemistry: The Kendall Award Addresses (Washington, D.C., 1973), 247–255. The Vinograd collection at the California Institute of Technology archives contains twenty-five years of his life.

II. Secondary Literature. For obituaries, see William R. Bauel in Engineering and Science, 40 (1976), 26–27; and Norman Davidson in Nature, 263 (1976), 178. A brief biography is in McGraw-Hill Modern Scientists and Engineers, III (New York, 1980), 256–257. A memorial issue of Nucleic Acids Research, 4 , no. 5 (1977), includes contributions from many former students and collborators. For a more detailed discussion of Vinograd’s contriburions to the study of nucleic acids, see V. A. Bloomfield, D. M. Crothers, and I. Timoco, Jr., Physical Chemistry of Nucleic Acids (New York, 1977).

William J. Hagan, Jr.