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 giving it a like or a comment, or subscribing
to the channel.
Thanks again for watching!