Alfred Day Hershey

Alfred Day Hershey (1908-1997) shared the Nobel Prize in medicine for his research on viruses.

By seeking to understand the reproduction of viruses, the simplest form of life, Alfred Day Hershey made important discoveries about the nature of deoxyribonucleic acid (DNA) and laid the groundwork for modern molecular genetics. Highly regarded as an experimental scientist, Hershey is perhaps best known for the 1952 "blender experiment" that he and Martha Chase conducted to demonstrate that DNA, not protein, was the genetic material of life. This discovery stimulated further research into DNA, including the discovery by James Watson and Francis Crick of the double-helix structure of DNA the following year. Hershey's work with bacteriophages, the viruses that prey on bacteria, was often carried out in loose collaboration with other scientists working with bacteriophages. Hershey shared the Nobel Prize in Physiology or Medicine in 1969 with Max Delbrück and Salvador Edward Luria. The Nobel Committee praised the three scientists for their contributions to molecular biology. Their basic research into viruses also helped others develop vaccines against viral diseases such as polio.

Hershey was born on December 4, 1908, in Owosso, Michigan, to Robert Day Hershey and Alma Wilbur Hershey. His father worked for an auto manufacturer. Alfred attended public schools in Owosso and nearby Lansing. He received his B.S. in bacteriology from Michigan State College (now Michigan State University) in 1930 and his Ph.D. in chemistry from the same school in 1934. As a graduate student, Hershey's interest in bacteriology and the biochemistry of life was already evident. His doctoral dissertation was on the chemistry of Brucella, the bacteria responsible for brucellosis, also known as undulant fever. Undulant fever is transmitted to humans from cattle and causes recurrent fevers and joint pain. After receiving his Ph.D., Hershey took a position as a research assistant in the Department of Bacteriology at the Washington University School of Medicine in St. Louis. There he worked with Jacques Jacob Bronfenbrenner, one of the pioneers in bacteriophage research in the United States. During the sixteen years he spent teaching and conducting research at Washington University, from 1934 to 1950, Hershey was promoted to instructor (1936), assistant professor (1938), and associate professor (1942).

Bacteriophages--known simply as phages--had been discovered in 1915, only nineteen years before Hershey began his career. Phages are viruses that reproduce by preying on bacteria, first attacking and then dissolving them. For scientists who study bacteria, phages are a source of irritation because they can destroy bacterial cultures. But other scientists are fascinated by this tiny organism. Perhaps the smallest living thing, phages consist of little more than the protein and DNA (the molecule of heredity) found in a cellular nucleus. Remarkably efficient, however, phages reproduce by conquering bacteria and subverting them to the phage particles' own needs. This type of reproduction is known as replication. Little was known about the particulars of this process when Hershey was a young scientist.

By studying viral replication, scientists hoped to learn more about the viral diseases that attack humans, like mumps, the common cold, German measles, and polio. But the study of bacteriophages also promised findings with implications that reached far beyond disease cures into the realm of understanding life itself. If Hershey and other researchers could determine how phages replicated, they stood to learn how higher organisms--including humans--passed genetic information from generation to generation.

Exposing the Secret Life of Viruses

Hershey's study of phages soon yielded several discoveries that furthered an understanding of genetic inheritance and change. In 1945 he showed that phages were capable of spontaneous mutation. Faced with a bacterial culture known to be resistant to phage attack, most, but not all, phages would die. By mutating, some phages survived to attack the bacteria and replicate. This finding was significant because it showed that mutations did not occur gradually, as one school of scientific thought believed, but rather occurred immediately and spontaneously in viruses. It also helped explain why viral attack is so difficult to prevent. In 1946 Hershey made another discovery that changed what scientists thought about viruses. He showed that if different strains of phages infected the same bacterial cell, they could combine or exchange genetic material. This is similar to what occurs when higher forms of life sexually reproduce, of course. But it was the first time viruses were shown to combine genetic material. Hershey called this phenomenon genetic recombination.

Hershey was not the only scientist who saw the potential in working with bacteriophages. Two other influential scientists were also pursuing the same line of investigation. Max Delbrück, a physicist, had been studying phages in the United States since he fled Nazi Germany in 1937. Studying genetic recombination independently of Hershey, he reached the same results that Hershey did in the same year. Similarly, Salvador Edward Luria, a biologist and physician who immigrated to the United States from Italy in 1940, had independently confirmed Hershey's work on spontaneous mutation in 1945. Although the three men never worked side by side in the same laboratory, they were collaborators nonetheless. Through conversation and correspondence, they shared results and encouraged each other in their phage research. Indeed, these three scientists formed the core of the self-declared "phage group," a loose-knit clique of scientists who encouraged research on particular strains of bacteriophage. By avoiding competition and duplication, the group hoped to advance phage research that much faster.

The "Blender Experiment"

In 1950 Hershey accepted a position as a staff scientist in the department of genetics (now the Genetics Research Unit) of the Carnegie Institute at Cold Spring Harbor, New York. It was at Cold Spring Harbor that Hershey conducted his most influential experiment. Hershey wished to prove conclusively that the genetic material in phages was DNA . Analysis with an electron microscope had showed that phages consist only of DNA surrounded by a protein shell. Other scientists' experiments had revealed that during replication some part of the parental phages was being transferred to their offspring. The task before Hershey was to show that it was the phage DNA that was passed on to succeeding generations and that gave the signal for replication and growth.

Although Hershey was not alone in having reached the belief that DNA was the stuff of life, many scientists were unconvinced. They doubted that DNA had the complexity needed to carry the blueprint for life and believed instead that the genetic code resided in protein, a far more elaborate molecule. Furthermore, no one had yet demonstrated the technical skill needed to design an experiment that would answer the question once and for all.

With Martha Chase, Hershey found a way to determine what role each of the phage components played in replication. In experiments done in 1951 and 1952, Hershey used radioactive phosphorus to tag the DNA and radioactive sulfur to tag the protein. (The DNA contains no sulfur and the protein contains no phosphorus.) Hershey and Chase then allowed the marked phage particles to infect a bacterial culture and to begin the process of replication. This process was interrupted when the scientists spun the culture at a high speed in a Waring blender.

In this manner, Hershey and Chase learned that the shearing action of the blender separated the phage protein from the bacterial cells. Apparently while the phage DNA entered the bacterium and forced it to start replicating phage particles, the phage protein remained outside, attached to the cell wall. The researchers surmised that the phage particle attached itself to the outside of a bacterium by its protein "tail" and literally injected its nucleic acid into the cell. DNA, and not protein, was responsible for communicating the genetic information needed to produce the next generation of phage.

Clearly DNA seemed to hold the key to heredity for all forms of life, not just viruses. Yet while the blender experiment answered one question about DNA, it also raised a host of other questions. Now scientists wanted to know more about the action of DNA. How did DNA operate? How did it replicate itself? How did it direct the production of proteins? What was its chemical structure? Until that last question was answered, scientists could only speculate about answers to the others. Hershey's achievement spurred other scientists into DNA research.

In 1953, a year after Hershey's blender experiment, the structure of DNA was determined in Cambridge, England, by James Dewey Watson and Francis Harry Compton Crick. Watson, who was only twenty-five years old when the structure was announced, had worked with Luria at the University of Indiana. For their discovery of DNA's double-helix structure, Watson and Crick received the Nobel Prize in 1962.

Career Honored with a Belated Nobel Prize

Hershey, Delbrück, and Luria also received a Nobel Prize for their contributions to molecular biology, but not until 1969. This seeming delay in recognition for their accomplishments prompted the New York Times to ask in an October 20, 1969, editorial: "Delbrück, Hershey and Luria richly deserve their awards, but why did they have to wait so long for this recognition? Every person associated with molecular biology knows that these are the grand pioneers of the field, the giants on whom others--some of whom received the Nobel Prize years ago--depended for their own great achievements." Yet other scientists observed that the blender experiment merely offered experimental proof of a theoretical belief that was already widely held. After the blender experiment, Hershey continued investigating the structure of phage DNA. Although human DNA winds double-stranded like a spiral staircase, Hershey found that some phage DNA is single-stranded and some is circular. In 1962 Hershey was named director of the Genetics Research Unit at Cold Spring Harbor. He retired in 1974 and died of cardiopulmonary failure at the age of 88 on May 22, 1997.

Hershey was "known to his colleagues as a very quiet, withdrawn sort of man who avoids crowds and noise and most hectic social activities," according to the report of the 1969 Nobel Prize in the October 17, 1969, New York Times. His hobbies were woodworking, reading, gardening, and sailing. He married Harriet Davidson, a former research assistant, on November 15, 1945. She later became an editor of the Cold Spring Harbor Symposia on Quantitative Biology. She and Hershey had one child, a son named Peter Manning. Born on August 7, 1956, Peter was twelve years old when Hershey won the Nobel Prize.

In addition to the Nobel Prize, Hershey received the Albert Lasker Award of the American Public Health Association (1958) and the Kimber Genetics Award of the National Academy of Sciences (1965) for his discoveries concerning the genetic structure and replication processes of viruses. He was elected to the National Academy of Sciences in 1958.

Historical Context

• The Life and Times of Alfred Day Hershey (1908-1997)
• At the time of Hershey's birth:
• The Christian Science Monitor began publication
• The Federal Bureau of Investigation (FBI) was created
• The Grand Canyon National Monument was created
• The times:
• 1914-1918: World War I
• 1939-1945: World War II
• 1950-1953: Korean War
• 1957-1975: Vietnam War
• 1983: American invasion of Grenada
• 1991: Persian Gulf War
• Hershey's contemporaries:
• Amelia Earhart (1898-1932) American aviator
• E.B. White (1899-1985) American writer
• Hans Krebs (1900-1981) British biochemist
• Ayn Rand (1905-1982) Russian-American writer
• Laurence Olivier (1907-1989) British actor
• Edward Teller (1908-) American physicist
• Mel Blanc (1908-1989) American entertainer
• Lyndon Baines Johnson (1908-1973) American president
• Willard Libby (1908-1980) American chemist
• Selected world events:
• 1909: NAACP was founded
• 1912: Jim Thorpe won the decathlon in the Olympic games
• 1920: Prohibition began in the United States
• 1929: The U.S. Stock Market Crash started the Great Depression
• 1941: Penicillin was purified and proven to fight bacterial infections
• 1945: Television was licensed for commercial use in the United States
• 1954: The U.S. Supreme Court declared segregation in public schools unconstitutional
• 1961: The Bay of Pigs invasion of Cuba failed
• 1973: The United States Supreme Court legalized abortion
• 1981: IBM introduced its first personal computer

Further Reading

• Fox, Daniel M., editor, Nobel Laureates in Medicine or Physiology: A Biographical Dictionary, Garland, 1990.
• Magner, Lois N., History of the Life Sciences, Dekker, 1979.
• McGraw-Hill Modern Scientists and Engineers, McGraw-Hill, 1980.
• Wasson, Tyler, editor, Nobel Prize Winners, H. W. Wilson, 1987.

• New York Times, October 17, 1969, p. 24; October 20, 1969, p. 46.
• Science, October 24, 1969, p. 479-481.
• "Three Americans Share Nobel Prize for Medicine for Work on Bacteriophage," in Chemical and Engineering News, October 27, 1969, p. 16.
• Time, October 24, 1969, p. 84.