Norton David Zinder

American virologist

• Born: November 7, 1928; New York, New York
• Died: February 3, 2012; New York, New York

As a graduate student, twentieth-century American virologistNorton Zinder discovered transduction, the process by which genetic material is transferred between bacteria by bacteriophage (bacterial viruses). Later in his career, he discovered the first bacteriophage in which RNA was the genetic material.

Primary field: Biology

Specialties: Genetics; virology; microbiology

Early Life

Norton David Zinder was born November 7, 1928. He was the first of two sons of Harry Zinder, a local manufacturer, and Jean Gottesman Zinder. Following his early education in the New York public school system, he attended the Bronx High School of Science, founded in 1938 to provide education for gifted students in science and mathematics. He graduated in 1944 at the age of fifteen.

Zinder enrolled at Columbia University in New York City. He received his bachelor’s degree in biology at the age of eighteen in 1947. While an undergraduate at Columbia, Zinder spent time in the zoology laboratory of biologist Francis J. Ryan. Among Ryan’s former students was molecular biologist Joshua Lederberg, who by then was on the faculty at the University of Wisconsin, and it was Ryan who helped Lederberg apply techniques while working with the bread mold Neurospora to a system utilizing Escherichia coli. Ryan encouraged Zinder to pursue his postgraduate work at the University of Wisconsin in order to work with Lederberg.

Life’s Work

Zinder joined Lederberg’s laboratory in 1948. Lederberg had recently completed his graduate work with geneticist Edward Tatum and had codiscovered bacterial conjugation, the transfer of genetic material between cells. Lederberg had carried out this work using the bacterium Escherichia coli (E. coli), and was interested in determining whether the process could also take place among other species of bacteria.

Zinder began this work with the bacterium Salmonella, chosen in part because of the large number of available mutants. The experimental method was similar to that previously used by Lederberg for E. coli, crossing two different strains that had different amino acid nutritional requirements and observing whether recombinants were produced that were capable of synthesizing those amino acids. In the process of conjugation, it was thought that the bacteria must come into contact with each other for the genetic information to pass. However, Zinder found in his experiments that contact was not necessary; the two different strains could even be kept separate using a filter between them. Zinder’s interpretation was that something physical was passing through the filter from one cell to another. The agent was shortly identified as a bacteriophage, a bacterial virus that was incorporating fragments of DNA from one strain and passing them to the second strain upon infection. Lederberg termed the process transduction. The same phenomenon was subsequently demonstrated in other species of bacteria.

In December 1949, Zinder married Marilyn Estreicher. Their fifty-five year marriage lasted until her death in 2004. The couple had two sons.

After receiving his PhD at Wisconsin in Medical Microbiology in 1952, Zinder accepted an offer as Assistant Professor at the Rockefeller Institute in New York, where he remained for the rest of his professional career. In 1960, Timothy Loeb joined Zinder’s laboratory as a graduate student. Loeb was interested in whether bacteriophage existed that were “male” specific and were capable of infecting the pilus on E. coli bacteria, the means by which conjugation took place. Since E.coli was found in sewage, a logical place to search for such bacteriophage was at the sewage plant in New York. Loeb quickly found seven types of such phage, which he and Zinder termed f1 (for fertility) through f7. F1 was found to contain single-stranded DNA as its genetic material, but f2 through f7 all contained RNA as genetic material, the first such bacteriophage demonstrated to contain RNA. Zinder found that the viral RNA was not only the genome, but that it served as its own messenger RNA, associating with ribosomes for translation into proteins.

In 1964, Zinder was promoted to professor of genetics at the institute, and a decade later he was promoted to John D. Rockefeller, Jr. Professor of Molecular Genetics. That same year saw his appointment as chair of the committee for evaluation of the Virus Cancer Program. The Zinder Report’s recommendation for altering the funding process resulted in a significant reorganization of the cancer program. In 1974, Zinder was also among those expressing concern about hazards associated with the new technology of recombinant DNA. The 1975 Asilomar Conference provided guidelines for such work.

During the late 1980s, scientists began work on what became known as the Human Genome Project, the goal of which was to sequence the entire human genome. Two figures stood at the forefront of the proposed project: James Watson, Nobel laureate for his role in determining the structure of DNA, and J. Craig Venter, biochemist and physiologist who entered the project as a private entrepreneur. The concern among many scientists was that if the project was publicly funded through research grants, the funding would occur at the expense of other equally worthwhile projects. At the time it was believed that relatively little of the human genome was relevant and that most consisted of unread sequences considered “junk.” Zinder repeatedly pushed for serious consideration by funding committees and was ultimately successful. The presence of Venter as a private citizen duplicating the work that Watson hoped to lead was also a concern. In 2000, Zinder negotiated an understanding between the different parties that allowed the project to continue.

Zinder died February 3, 2012 in New York at the age of eighty-three.

Impact

Zinder’s discovery of transduction represented the third mechanism of transfer of genetic information between bacteria. As noted by other scientists in the field of genetics, several aspects common to each of these mechanisms involving movement of genetic elements in bacteria set them apart from genetic recombination in eukaryotic organisms. First, recombination did not involve the entire genome but only portions of the DNA. The discovery of transduction altered the thinking applied to the role of viruses. In addition to possibly killing the bacterial cells they infect, viruses could also serve as vectors for the transfer of genetic material.

Within several years, two forms of transduction were shown to take place. Generalized transduction, as first described by Zinder, involved the transfer of random fragments of DNA, largely anything that was packaged during bacteriophage assembly. The discovery of lysogeny in bacteria, the integration of bacteriophage into the host genome usually at nonrandom sites, allowed for what became known as specialized transduction, the transfer of only those genes adjacent to the site of integration in the host.

The discovery of transduction provided one more technique for fine-structure genetic mapping of bacteria. By determining which genes co-transduced in the same fragment, it became possible to observe which particular genetic markers were adjacent to each other in the bacterial genome. Among the first of these discoveries was that genes that regulate specific metabolic pathways or regulate the expression of genes within a pathway are often closely linked to each other on the bacterial genome in an area that became known as the operon. For example, in the early 1960s, French molecular biologists François Jacob and Jacques Monod produced their model of regulation of the lactose operon by means of transducing specific genes within the operons of Escherichia coli and Shigella. The model they produced became the basis for Jacob and Monod being awarded Nobel Prizes in Physiology or Medicine in 1965.

Bibliography

Brock, Thomas. The Emergence of Bacterial Genetics. Woodbury, New York: Cold Spring Harbor Lab. P, 1990. Print. Reviews the history behind understanding bacterial genetics. Zinder’s role in the discovery of transduction is discussed.

Crotty, Shane. Ahead of the Curve: David Baltimore’s Life in Science. Berkeley: U of California P, 2001. Print. Biography of Nobel laureate David Baltimore. Addresses the significance of Zinder’s role in the discovery of RNA phage.

Witkowski, Jan. The Inside Story: DNA to RNA to Protein. Woodbury, New York: Cold Spring Harbor Lab. P, 2005. Print. Includes a discussion of Zinder’s discovery of RNA phage, which was among the first indications RNA could also serve as genetic material.