Norton Zinder, pioneering molecular geneticist, dies at 83

Norton D. Zinder, a geneticist and microbiologist whose research on the genetics of bacteria and on the properties of bacteriophages — viruses that infect bacteria — provided important information on the mechanisms of heredity, died Friday, February 3 after a long illness. He was 83.

Zinder was a John D. Rockefeller Jr. Professor Emeritus at The Rockefeller University, where he spent his entire research career.

His first major discovery, transduction in bacteria, resulted from experiments performed when he was a graduate student at the University of Wisconsin, in collaboration with the late Nobel Prize winner Joshua Lederberg. In 1949, the two began a series of investigations, based on the 1946 findings of Lederberg and Edward Tatum, that two strains of the bacillus Escherichia coli could mate under certain conditions.

Zinder and Lederberg attempted to induce mating in another species of bacterium, Salmonella typhimurium. The expected colonies of the new type of cells appeared, but further analysis revealed that they were the product not of sexual mating, but of a hitherto unknown process, now designated “transduction,” whereby bacteriophages act as carriers of genetic material from donor to recipient bacteria.

These experiments and the resulting methodology made transduction a powerful tool for the study of bacterial genetics and for such applied problems as antibiotic resistance and bacterial classification. Further research enabled Zinder and his colleagues to develop techniques for mating Salmonella which allow for the specific differentiation of donor (male) and recipient (female) bacteria.

Upon moving to Rockefeller, Zinder further pursued his studies of transduction and confirmed that transduction is mediated by viral particles exchanging their own DNA for bacterial DNA, which they then carry. This discovery anticipated the use of recombinant DNA in the 1970s.

In 1960, Zinder and Timothy Loeb, then a graduate student in his laboratory, discovered seven new bacterial viruses specific for E. coli males. The viruses, which were named f1 through f7 (f for fertility factor), proved to be unique. F1 was found to contain a single strand of DNA as its genetic material, and f2 through f7 proved to be the first known RNA-containing bacteriophages.

The discovery of the RNA phages had great importance in studies of fundamental genetic processes because their unusually small size — smaller than the polio virus and with half its genetic material — made it possible to identify each submolecule of their genetic code.

Additional investigations of the RNA bacteriophages led Zinder and his laboratory group to the first demonstration, in 1962, that virus replication in the RNA phage is not dependent on DNA — that in fact, the RNA phage f2 acts both as its own genetic material and as a template for directing protein synthesis. This research provided further evidence that ribonucleic acid carries the blueprint for the manufacture of protein. Also, with the use of phage RNA, many details of protein biosynthesis, including its initiation and termination, were worked out.

Zinder’s research on molecular and physiological genetics emphasizes genetic recombination of the bacteriophage f1 and the physical mapping of its genome by means of restriction enzymes (agents which cleave genetic material) as well as nucleotide sequence analyses of messenger RNA from both prokaryotes and eukaryotes. (Prokaryotes are organisms, like bacteria, that do not have true nuclei.) These studies were designed to explore in detail the mechanism of gene action and control in a small, finite organism. In addition, they provided tools for the detailed study of the mechanism of action of these sequences and structure-specific enzymes, which are currently in wide use.

Zinder also discovered the phenomenon of bacterial restriction-modification and described the class of enzymes responsible for that activity, the Type I restriction endonucleases. His work paved the way for the subsequent identification of the site-specific restriction endonucleases, Type II restriction endonucleases, that were critical to the development of recombinant DNA technologies.

Born in New York City on November 7, 1928, Zinder received an A.B. degree from Columbia University in 1947 and a Ph.D. from the University of Wisconsin in 1952, the year he joined The Rockefeller University — then known as The Rockefeller Institute for Medical  Research — as an assistant. He was appointed associate in 1956, associate professor in 1958, professor in 1964 and John D. Rockefeller Jr. Professor in 1977. From 1993 to 1995, he served as the university’s dean of graduate and postgraduate studies.

He was an American Cancer Society Scholar from 1956 to 1958. He was the recipient of the Eli Lilly Award in Microbiology in 1962 and was honored by the National Academy of Sciences in 1966 with its United States Steel Foundation Award in molecular biology “for the discovery of RNA phages and for the analysis of the mechanisms of their replication.” In 1969, he was awarded the Medal of Excellence by Columbia University, the Scientific Freedom and Responsibility award from the American Association for the Advancement of Science in 1982 and an honorary degree from the University of Wisconsin, Madison, in 1990.

He served on the National Academy of Sciences Board of Army, Navy, Science and Technology, on the Report Review Panel of the National Academy of Sciences, and on visiting committees at Harvard and Princeton Universities. He was chairman of the Committee on Industry-University Relationships, COGENE, and a trustee of Cold Spring Harbor Laboratory.

Zinder was an active spokesman on the responsibilities of scientists. In 1973 the National Cancer Advisory Board of the National Institutes of Health appointed him chairman of a committee to evaluate the National Cancer Institute’s nine-year-old Virus Cancer Program. The committee’s findings, known as the Zinder Report, resulted in a major reorganization of the program. He was one of the original members of the Committee on Recombinant DNA Molecules of the National Research Council of the National Academy of Sciences from 1974 to 1975. From 1982 to 1984 he chaired a committee of the National Academy of Sciences and the Nuclear Regulatory Commission which made recommendations on the technical means for disposal of the large U.S. stockpile of chemical weapons. He was a founding member of the Human Genome Organization.

The author of numerous scientific papers, Zinder edited the book, RNA Phages (Cold Spring Harbor Press, 1975) and he served as an associate editor of Virology and section editor of Intervirology. He was elected to membership in the National Academy of Sciences in 1969. He was a member of the American Academy of Arts and Sciences, the American Society of Biological Chemists, the Genetics Society of America, the American Society of Microbiology, the American Association for the Advancement of Science and Sigma Xi.