HERSHEY, Alfred Day

(b. 4 December 1908 in Owosso, Michigan; d. 22 May 1997 in Syosset, New York), Nobel Prize–winning bacteriologist, biochemist, and molecular geneticist whose work with bacteriophages helped prove that DNA is the source of heredity, thus paving the way to an understanding of viral infections.

Hershey was the son of Robert Day Hershey, an auto manufacturer, and Alma Wilbur, a homemaker. He attended public schools in Owosso and Lansing, Michigan, and Michigan State College, from which he received a B.S. degree in bacteriology in 1930 and a Ph.D. in chemistry in 1934. He then took a research assistant position at the Washington University School of Medicine in St. Louis, where he became an associate professor in 1942 and taught until 1950. On 15 Nov. 1945 Hershey married Harriet Davidson, a former research assistant who later became editor of a biological review; they had one son.

Hershey focused his research on bacteriophages (commonly known as phages), small particles made of a protein shell and a DNA molecule that are found in the nucleus of cells. Phages are viruses that can infect bacteria, turning the latter into virus manufacturers and subsequently killing them. While working in St. Louis, Hershey met the physicist Max Delbrück and the biologist and physician Salvador E. Luria, and the three researchers formed the basis of what would later be known as the "phage group," scientists who shared their phage research results to advance science.

In 1950 Hershey moved to the department of genetics of the Carnegie Institution of Washington (now the Carnegie Institute) in Cold Spring Harbor, New York. It was there that he carried out one of modern biology's most famous experiments, in 1952. Together with his assistant Martha Chase, Hershey tagged the DNA of phage T2 with radioactive phosphorous (DNA contains a lot of phosphorous, proteins have very little), and the protein shell of another batch of the same phage was labeled with radioactive sulfur (DNA contains no sulfur). Using a kitchen blender to separate the infected bacteria from phage particles clinging to the outside walls of the bacteria, Hershey and Chase found the radioactive DNA inside the bacteria, while the radioactive protein shell stayed outside. This provided the answer to a question that scientists had been asking for several decades: Which is the hereditary material, protein or DNA? Most researchers had assumed that proteins, owing to their greater complexity, were the hereditary molecules. The results of the blender experiment surprised even Hershey. His proof heralded the explosion of genetics that has changed life as we know it today. According to James Watson, the blender experiment was the final push that he and his research partner Francis Crick needed to determine the structure of DNA.

Following the blender experiment, Hershey continued to work with phages and supplied other molecular biologists with valuable tools and insights. To characterize phage DNA further, he needed to be able to extract and purify it from a phage. In the 1950s and early 1960s there were no techniques to achieve this end, so Hershey and his colleagues set out to develop them. As Hershey would say in his Nobel lecture on 12 December 1969, "Without knowing it, we were entering one of those happy periods during which each technical advance yields new information." By 1961 Hershey had discovered a way to extract both intact and fractured DNA. His method, with further refinements, continues to be used by researchers today.

Once he found the way to purify DNA and obtained controlled fractures of the molecule, Hershey went on to prove that T2 DNA was a single linear molecule. Because this conclusion seemed at odds with observations of another phage, T4, efforts to reconcile the seeming contradictions led to the discovery that phage DNA can be circular. Hershey's final 1965 proof of circular viral DNA was, in James Watson's words, "a bombshell result, because circular molecules had 2 years before been hypothesized as an intermediate in the integration of I [phage ? I] DNA molecules into bacterial chromosomes." Hershey helped show how viruses infect bacteria, and his finding has been instrumental in the later development of the recombinant DNA technique. Recombinant DNA has saved countless lives around the world by enabling the production of needed compounds, such as insulin, cheaply and in large quantities. Phage ? I has been widely used in recombinant DNA techniques.

In 1962 Hershey was appointed director of the genetics research unit at Cold Springs Harbor, where he remained until his retirement in 1973. He continued to characterize phage DNA along with colleagues in his lab. Experiments by Gisela Mosig in 1964 helped create a map of genetic markers of phage T4. Mosig credited Hershey's pioneering work when she said: "Everything we do now is really based on that knowledge [that DNA is the hereditary molecule]." In 1963 and 1968, respectively, his colleagues Fred Frankel and Rudy Werner investigated the intracellular structure of certain T phages and thus helped researchers gain insight into how phage recombination works.

Along with giving researchers insights into the structure and characteristics of phage DNA, Hershey developed laboratory methods for handling and measuring DNA. These methods were adopted by molecular biology and genetics researchers all over the world. In 1969 Hershey, Delbrück, and Luria were awarded the Nobel Prize in physiology or medicine for their contributions to molecular biology, an honor that many thought they should have received earlier. Hershey died of heart failure.

Although Hershey's work in the 1960s may not have been as earth shattering as his blender experiment in 1952, the swift pace of developments in the field of genetics, beginning with Watson and Crick's discovery of the double helix and continuing through recombinant DNA and beyond, started with this single experiment. Although Hershey is typically remembered for that one achievement, his continuing work and collaboration with others on the mechanisms of phage infection, both before and after 1952, were instrumental in laying the basis for vaccines for such diseases as polio and mumps and expanded our understanding of viral infections. Hershey was one of the founders of molecular biology, and during the 1960s he continued to advance this new discipline. His influence on the burgeoning sciences of genetics and molecular biology went beyond the lab. In addition to his own papers, he wrote review articles that educated others.

Biographies of Hershey include Franklin Stahl, We Can Sleep Later: Alfred D. Hershey and the Origins of Molecular Biology (2000). Articles on Hershey's life include John Cairns, "Alfred Hershey (1908–1997): One of the Founding Fathers of Molecular Biology," Nature 388 (1997), and A. Campbell and F. W. Stahl, "Alfred D. Hershey," Annual Review of Genetics 32 (1998): 1–6. Obituaries are in the New York Times (24 May 1997), Times (London) (2 June 1997), and Independent (London) (7 June 1997).

Adi R. Ferrara