Welcome back to Bogobiology! In this video, we’ll be discussing the classic
Hershey and Chase Experiment and how it proved conclusively that DNA was the molecule of
heredity in 1952. Remember that there are four major groups
of biomolecules; carbohydrates, lipids, proteins and nucleic acids. In the first half of the 20th century, scientists
still weren’t entirely in agreement about which biomolecule passed genetic information
from parent to offspring. Many believed it to be proteins because they
are so large, structurally complex, and have so much variety. Dr. Alfred Hershey and Dr. Martha Chase’s
now famous experiment was actually the third major investigation into what genes are made
of. They learned from the previous work of Frederick
Griffith in 1928 and Oswald Avery, Colin MacLeod and Maclyn McCarty in 1944. It’s important to know how each experiment
built upon those that came before in order to understand the experimental design. First, Frederick Griffith proved that some
sort of substance could be transferred between bacteria, which could change its properties
in a process we now call bacterial transformation. He called this
mysterious substance the “transformation principle” and demonstrated its power in
a famous experiment involving mice and pneumococcus bacteria. Harmless R-strain bacteria could acquire material
from dangerous R-strain bacteria and become deadly. However, at the time, Griffith didn’t know
what kind of molecule the transformation principle was. Second, Avery, MacLeod and McCarty performed
a series of experiments to isolate the transformation principle, and analyzed it extensively. They found that the mysterious substance was
most chemically similar to DNA. Then, they methodically destroyed proteins,
RNA and DNA and discovered that disabling DNA prevents bacterial transformation from
occurring. However, the scientific community disputed
Avery’s results, believing that trace amounts of transformation principle could have contaminated
their samples of DNA, and that proteins could still be the molecules of heredity. If you’d like more details about Griffith’s
or Avery’s experiments, I’ve left links to tutorials on their work in the video description,
as well as the links to the guided notes for each video. Hershey and Chase picked up where Avery and
his colleagues left off, and set out to prove once and for all whether the molecule of heredity
was protein or DNA. They chose to do their work by harnessing
a simple virus called a T2 bacteriophage. These bacteriophages have several helpful
properties, including the fact that they reproduce very quickly and are only made up of two of
the "Big Four"; nucleic acids and proteins. Hershey and Chase had previously studied the
properties of these bacteriophages and had concluded that the protein formed a type of
protective coating or “shell” around the nucleic acids. Bacteriophages naturally reproduce by attaching
to the outside of a host cell. In the case of the T2, they attack e coli. Then they inject their genetic material into
it, which hijacks the internal workings of the cell, while the empty protein coat stays
on the outside. This empty shell is sometimes called a “protein
ghost”. The DNA from the bacteriophage then causes
the cell to stop whatever it was doing and begin producing identical copies of the original
bacteriophage. The host cell then explodes, releasing all
of the new bacteriophages, which then go out and infect even more cells. Hershey and Chase harnessed the viral life
cycle to prove which of the two contenders was actually responsible for inheritance;
proteins or nucleic acids. Hershey and Chase used two groups of bacteriophages,
and made a single component radioactive in each one to keep track of what it was doing. In one group, they tested the viral protein
coat on the outside, and in the other group they tested the nucleic acids on the inside
of the virus. They knew that whichever part was responsible
for genetic inheritance would create more radioactive bacteriophages, and the other
would not. Proteins and nucleic acids contain some of
the same elements such as Carbon, Hydrogen, Oxygen and Nitrogen. However, they differ in that proteins can
contain sulfur, and nucleic acids contain phosphorous. The researchers tracked the elements that
were unique to each biomolecule. In proteins, they replaced the sulfur with
a radioactive isotope known as sulfur 35. Since sulfur is not found in nucleic acids
but is found in some amino acids, they were only marking the protein coat. In the nucleic acids, they replaced the naturally-occurring
phosphorus in the nucleic acids with a radioactive type of phosphorus called phosphorus 32. Since there was no phosphorus found in the
protein coat, the only thing they were marking in the second group was the nucleic acids. You might say that the sulfur and the phosphorous
each got a major glow up. Once the appropriate molecules were tagged,
the experiment consisted of three major steps; infection, blending, and centrifugation. In the infection step, Hershey and Chase then
allowed each type of bacteriophage to infect a host cell to see whether the radioactive
proteins or the radioactive nucleic acids would make radioactive bacteriophages. Next, in the blending step, they used a high
speed blender to jiggle the e coli cells enough to shake off the empty protein shell from
the outside. (This is why this experiment is sometimes
affectionately referred to as the “Blender Experiment”). This created a mixture of liquid, phage parts
and bacteria called a “suspension”. Finally, in the centrifugation, they spun
this mixture in a centrifuge so that the heavier bacteria condensed and formed a pellet at
the bottom of the test tube. Since the virus particles were much smaller
and lighter, they remained suspended in the liquid or the “supernatant”. Experiment results:
Hershey and Chase measured the level of radioactivity in the liquid vs in the pellet to see where
the radioactivity had ended up. Hershey and Chase knew that the virus had
transferred its genetic material, whatever it was, into the bacterial cells. Because the bacterial cells were heavier,
they would end up in the pellet along with the injected radioactive material, after centrifugation. If proteins were the molecule of inheritance,
the pellet would be more radioactive than the supernatant in the protein group. If nucleic acids were the molecule of inheritance,
the pellet would be more radioactive than the supernatant in the nucleic acid group. When they tested the two groups, they found
that the supernatant was more radioactive in the protein group, and the pellet was more
radioactive in the nucleic acid group, indicating that the viral DNA had entered the cell. This provided very compelling evidence that
nucleic acids, not proteins, were the molecule of inheritance. Because the experiment was conducted using
bacteriophages, some scientists were still skeptical of its implications. Some believed that, while Hershey and Chase
had proved DNA was the genetic material for viruses, it might not be the genetic material
for more complex organisms. However, the scientific community did ultimately
accept their findings. Dr. Alfred Hershey would eventually receive
the 1969 Nobel Prize in Medicine for this work. However, the Nobel Committee (frustratingly)
excluded Dr. Martha Chase, and Alfred Hershey did not acknowledge Chase’s role in discovering
that DNA is the molecule of heredity in his acceptance speech. That wraps up our discussion of Hershey and
Chase’s work. If you found this video useful, please consider
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