WORLD OF MICROBIOLOGY AND IMMUNOLOGY Hershey, Alfred Day269•
Bronfenbrenner, one of the pioneers in bacteriophageresearch
in the United States. During the sixteen years he spent teach-
ing 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 prey-
ing on bacteria, first attacking and then dissolving them. For
scientists who study bacteria, phages are a source of irrita-
tion 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 cel-
lular nucleus.
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 under-
standing life itself. If Hershey and other researchers could
determine how phages replicated, they stood to learn how
higher organisms—including humans—passed genetic infor-
mation from generation to generation.
Hershey’s study of phages soon yielded several discov-
eries that furthered an understanding of genetic inheritance
and change. In 1945, he showed that phages were capable of
spontaneous mutation. Faced with a bacterial cultureknown 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 mutationsdid not occur gradually, as one school of scien-
tific thought believed, but immediately and spontaneously in
viruses. It also helped explain why a 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 sim-
ilar to what occurs when higher forms of life sexually repro-
duce, 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 poten-
tial in working with bacteriophages. Two other influential sci-
entists 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 con-
firmed 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 con-
versation and correspondence, they shared results and encour-
aged 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 onparticular strains of bacteriophage. By avoiding competition
and duplication, the group hoped to advance phage research
that much faster.
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 conclu-
sively that the genetic material in phages was DNA. Analysis
with an electron microscopehad 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.
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 radioac-
tive phosphorus to tag the DNA and radioactive sulfur to tag
the protein. (The DNA contains no sulfur and the protein con-
tains 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 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 genera-
tion of phage.
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 struc-
ture was announced, had worked with Luria at the University
of Indiana. For their discovery of DNA’s double-helix struc-
ture, Watson and Crick received the Nobel Prize in 1962.
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 Timesto 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 recogni-
tion? 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 experi-
mental 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 dou-
ble-stranded like a spiral staircase, Hershey found that somewomi_H 5/6/03 3:20 PM Page 269