Karolinska Institutet has decided
to award the Nobel Prize in Physiology or Medicine for 1969
Max Delbrück, Alfred D. Hershey and Salvador E.
for their discoveries concerning "the replication mechanism and
the genetic structure of viruses".
Around 1940 Delbrück, Hershey and Luria became interested in
bacteriophage, a type of virus that infects bacteria, rather than
ordinary cells. They were trying to find a living system as
simple as possible, on which to study with hope of success,
fundamental life processes, first of all self-replication.
Bacteriophage soon revealed itself to be an object of choice for
such research. They worked out rigorous quantitative methods and
this turned bacteriophage research into an exact science. They
synchronized virus multiplication and were thus able to follow in
detail the various phases in the process. They studied what
happened in single cells and analyzed their results with advanced
statistical methods. They made a series of fundamental
discoveries, of which the following will be mentioned.
As a result of infection, both virus and cell undergo drastic
changes. The so-called cell-virus-complex behaves as an
essentially new system. The chemical activities of the cell are
reprogrammed. The virus loses its individuality and enters an
"eclipse" or "dark" phase, during which it can no longer be
identified as a particle. The metabolic activities which it
releases can lead in a matter of minutes to the formation of
hundreds of new virus particles.
The virus particle consists principally of nucleic acid
surrounded by a protein shell. At infection the nucleic acid is
injected by a simple but extremely efficient mechanism into the
cell, while the protein shell remains outside. The role of
nucleic acid as the carrier of the genetic information of the
virus was thus demonstrated. The discovery of numerous genetic
variants of the virus showed that the latter contained more than
a single gene. Soon after genetic recombination was discovered to
take place: two virus particles simultaneously infecting the same
cell can exchange parts of their strings of genes and give origin
to hybrid forms. This phenomenon made possible a detailed
analysis of the genetic structure of the virus. Thanks to the
short reproduction time of the virus and the large number of
progeny virus obtained, bacteriophage work, in a matter of hours,
can yield information that with other virus material might
require months or years.
The work of Delbrück, Hershey and Luria has had a great
impact on biology in general. Bacteriophages have served and
continue to serve as models for the more complicated and less
approachable systems represented by animal and human cells.
Delbrück, Hershey and Luria have set the solid foundations
on which modern molecular biology rests. Without their
contributions the explosive development of this field would have
been hardly possible. From the medical point of view, the
discoveries for which the award is now given first of all imply a
deeper insight into the nature of viruses and of virus diseases.
Indirectly they also bring about an increased understanding of
the mechanism of inheritance and of those mechanisms that control
the development growth and function of tissues and organs. Over
the years our debt of gratitude to the three leading figures of
bacteriophage research has continually increased.
Delbrück was trained as a physicist, but soon became
interested in biological problems. Already in 1933, in Berlin, he
had joined a research group that was experimenting on the
production of mutations in fruit-flies with different kinds of
radiations. This collaboration led to a quantum-mechanical model
of the gene, permitting, for example, estimations of gene size.
But there was little promise of further advance in the field as
long as complex organisms were used as experimental material.
Simpler biological systems had to be found.
A few years later, in the United States, after meeting a
colleague who was working with bacteriophage, he realized that
this might be an ideal material for the experimental attack of
the most fundamental biological problems, self-replication and
At about the same time, Luria, a research minded
physician, who had just come to the United States from Italy, was
using bacteriophages in radiobiological experiments of the kind
that the Berlin group had performed on fruit-flies. In the United
States, Delbrück and Luria became well acquainted with each
other and collaborated on several occasions. Together they gave
new impetus to research on bacteriophages.
Bacteriophages are a group of viruses that infect bacteria rather
than ordinary cells. They can multiply very rapidly and in very
large numbers. They are not pathogenic to man, hence can be
handled with rather simple bacteriological methods. Discovered as
early as 1915, bacteriophages had been the object of much work
over the years, but few results of biological or medical
importance had come from it. Delbrück and Luria introduced
into this field genetic concepts and rigorous quantitative
Between 1940 and 1945 they established the main outlines of
bacteriophage multiplication (duration of the infectious process,
number of progeny bacteriophages produced by an infected
bacterium, the various stages of the infectious process, etc.)
They introduced criteria for distinguishing mutation from other
modifications in both bacteriophage and bacteria. They began to
explore the interactions taking place when virus particles of two
different kinds infect the same bacterium.
Their work attracted the attention of Hershey, a
microbiological chemist, who had already used bacteriophages for
many years as antigens in his studies of immunological reactions.
At this time a very fruitful collaboration began to develop
between Delbrück, Hershey and Luria, and their laboratories.
No joint research program was implied. Rather, this collaboration
was based on a free exchange of information and material, on
avoiding duplication of efforts, and on refraining from any
unproductive form of scientific competition. A school, the
so-called "phage group" informally grew up around Delbrück,
Hershey and Luria, with a geographic center at the Biological Laboratory in Cold Spring
Harbor, where informal research conferences were often
In 1946 Hershey demonstrated the independence of different
mutation types occurring in the same virus: this was the first
indication that a virus may contain more than one gene. In the
same year Delbrück discovered an unexpected genetic
interaction between viruses infecting the same cell. Hershey
further advanced this work. He demonstrated that the phenomenon
was due to genetic recombination and that it could be used to
construct the genetic map of virus. Luria was able to support
this interpretation with experiments in which genetic damage
caused by radiation in bacteriophages could be repaired by gene
exchange following infection of the same host bacterium with
several damaged virus particles. These findings opened tremendous
possibilities of analyses of the structure of genetic
It was then known from the observations of several other
investigators that bacteriophage particles were made of protein
and nucleic acid, with the nucleic acid located inside the
particles and the protein outside. It had also been found that
relatively simple manipulations could split the two components.
Hershey posed the question of whether a similar splitting took
place in the course of infection. By using radioactive label in
the protein or in the nucleic acid, he was able to show (1952)
that only the nucleic acid of the virus entered the bacterium,
hence was sufficient for the complete reproduction of the
bacteriophage. The experiment demonstrated that the nucleic acid
of these viruses was their genetic material.
Hershey continued the work with a very thorough analysis of the
metabolic processes taking place in the bacterium following entry
of the virus nucleic acid. He succeeded in establishing the basic
picture of the infectious process of a bacteriophage in
biochemical terms. In the course of this work he uncovered the
very first indication of the special nucleic acid fraction
(messenger RNA) that is now known to act as information carrier
between genetic material and protein.
In later times Delbrück has made theoretical contributions
to the problem of how nucleic acid replicates, although his main
research interest has shifted from genetics to physiology. Luria
has investigated phenomena of conversion, in which a
bacteriophage carried by a bacterium in a semi-permanent
association produces certain changes in the properties of the
bacterium. These systems are used as models for similar
interactions in animal cells, where association with a virus can
cause the cell to become cancer-like. Hershey has developed new
techniques for the study of nucleic acid molecules. He has
demonstrated the interconversion of a linear nucleic acid
molecule to a ring-shaped one.
During the last 15 years the work on bacteriophage has had a
tremendous impact on virology, and has supplied material and
techniques which have been essential to the progress of molecular
biology. The basic sequence first demonstrated in bactoriophage
reproduction: splitting of the virus particle into nucleic acid
and protein, multiplication of the nucleic acid, synthesis of
specific viral protein, and reconstitution of progeny virus
particles from the new nucleic acid and the new protein is now
generally accepted as the basic pattern of reproduction of all
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MLA style: "Physiology or Medicine 1969 - Press Release". Nobelprize.org. Nobel Media AB 2014. Web. 19 Dec 2014. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/1969/press.html>
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