Turning the clock back to the 1940s and 50s, the scientific community was in the midst
of a debate about the nature of the hereditary material that is responsible for passing our
traits on to our children, to our children’s children, and so on for generations—pretty
existential question, right?. An experiment by Avery, MacCleod and McCarty in 1944 first
suggested that proteins were not responsible for heredity, as previously thought, and instead,
DNA was the culprit. However, given that their results flew in the face of the current thinking,
not everyone was convinced. In science, a great deal of evidence is needed before a
new scientific idea is accepted as fact. Therefore, in 1952, Alfred Hershey and Martha Chase carried
out experiments which addressed the same question was DNA the hereditary material? Or was
it protein? Or was it something else?
To solve this important puzzle, Hershey and Chase needed a simple model organism to solve
this complex question and a clever experiment. They chose the simplest organism possible-
a bacteriophage, which is a virus that infects bacteria. This virus looks a bit like a lunar
landing module, and attaches to the outside of the bacteria. It then injects a substance
into the bacteria to create many new copies of the virus. These newly
manufactured viruses are released when the bacteria bursts. So the substance injected
inside of the bacteria must contain the instruction manual for making new virus—it contains
the hereditary material. But what was this material that the virus injected into its
host? The answer to their question might shed light on the nature of heredity for all life
on earth!
Viruses consist of 2 things: a DNA core surrounded by a protein coat. Hershey and Chase needed
to figure out which of the two was injected into the bacteria. They ran two experiments,
and in each they labeled one of the components. For this labeling they used radioactive tags
– radioactive phosphate for the DNA, and radioactive sulfur for the protein. This was
an elegant method, because phosphate is only found in DNA, and not in the amino acids that
make up proteins, and sulfur is only found in proteins and not DNA.
After the viruses infected the bacteria, the researchers examined whether the radioactive
signal was detected inside the bacteria, or was left outside. To do so, they needed to
separate the bacteria from the viruses attached to their outsides, and did so using a Waring
blender (similar to that used for making milk shakes). Once separated, they then centrifuged
the sample - since bacteria are bigger they were centrifuged to the bottom while the smaller
viruses remained at the top of the tube.
When they prepared virus with sulfur-labeled protein and mixed it with bacteria, they found
that most of the radioactivity remained with the virus and did not enter the bacteria.
When they allowed the virus to replicate and collected the new viruses, less than 1% of
the protein radioactivity from the viral parents was found in the newly replicated virus, so
the protein was not being inherited.
On the other hand, when they performed the same experiment using virus with its DNA labeled
with phosphate, they found that most of the radioactive DNA was injected into the bacteria
from the attacking virus and much of this labeled DNA was inherited and passed on to
the new virus generation.
Hershey and Chase added to the mounting evidence pointing the finger at DNA as the hereditary
material, but they were aware that their experiments left a few unanswered questions – as experiments
often do! – and were cautious in their conclusions. From their observations, they stated that
DNA had ‘some function’ in the multiplication of the bacteria, whereas protein did not.
Word about the Hershey Chase experiment spread quickly and helped to convince many scientists
that DNA indeed was the molecule of heredity. And the remaining skeptics could not hold
out for much longer. A year later Watson and Crick published their model of the DNA double
helix which provided an elegant explanation for how DNA, with such a simple structure,
can be replicated and pass along information from parents to offspring.
The Hershey Chase experiment is considered a classic in biology because it tackled an
important question, with the use of a well-chosen model organism and elegant experimental design
in order to clearly distinguish between two competing hypotheses.