DNA is considered the molecule of life
and is now easily identified as a double helix.
However, figuring out its structure,
and how DNA works,
was not an easy task,
and just a little over 60 years ago
it was still a complete mystery.
Then, in 1953,
came Watson and Crick,
who, with the help from colleagues Rosalind Franklin and Maurice Wilkins,
discovered how the six billion base pairs
that make up our genetic material
are stored in the cell.
The DNA was actually a helix made of two strands.
This DNA was passed on from generation to generation
as a double helix.
Specific DNA bases,
which we call A, adenine; T, thymine;
G, guanine; and C, cytosine,
are found on both strands
and pair with each other in a conserved way.
A pairs with T, and G pairs with C.
Our DNA is made up of these four bases
in a variety of different orders
that code for all of life.
This is an amazing fact.
These four bases are the sole building blocks
for our six billion bases of genetic code,
which defines our identity as humans
and as individuals --
our height, hair color, disease susceptibility,
and much, much more.
Discovering the structure of DNA
was a very important first step
to understanding how this seemingly simple molecule
controls all of life.
However, one important question lingered.
When a cell divides,
the daughter cell will have the same DNA sequence
as the parental cell.
So, how does this happen?
How does one cell produce a second cell
with the same exact DNA sequence?
In other words, how does DNA replicate?
This is a fundamental question
that is the basis of life.
We all come from a single cell
that will produce an entire organism
with trillions of cells
that all have the exact same DNA sequence.
And we are able to have children that share our DNA,
because our eggs and sperm carry our DNA sequence.
Understanding how DNA replicates
and how all of our cells
can carry the same DNA sequence
is the basis for understanding development, inheritance,
heritability, and life.
In 1953, the question lingered.
How does DNA replicate?
There were a few theories -- three, actually.
One of them was conservative replication,
where a DNA molecule would get copied
and make a second, new, red DNA molecule.
The second was dispersive,
where the DNA molecule would be cut at various parts,
each of which would get copied -- here, in red --
and reattached to produce two DNA molecules.
And the third was semiconservative,
where two DNA strands would separate,
and each one would serve as a template to copy
a second, red strand,
thus producing two DNA molecules.
But which one was it?
Many scientists did not believe that two DNA strands
could separate
because of how strong a DNA molecule is,
so they were skeptical of the semiconservative model.
The only way to solve this was to create an experiment
to tell the new DNA strand from the old one.
So, two scientists, Matthew Meselson and Franklin Stahl,
had an idea to design an experiment
that would be known as the most beautiful experiment in biology.
Their findings are published in their article titled
"The replication of DNA in E. coli",
published in May 1958
in the Proceedings of the National Academy of Sciences.
These scientists used bacteria to answer the question of DNA replication,
since it could be easily grown in the laboratory.
They grew the cells in the presence of a specific type of nitrogen,
which is found in DNA,
that would make all of the DNA very heavy.
They used centrifugation,
which can separate things according to their weight.
Initially, all of the DNA in the cell was heavy
and was at the bottom of the tube,
since it was grown in heavy nitrogen.
Then, they started growing these cells
in the presence of light nitrogen
so all of the DNA made in subsequent cell divisions
would be lighter.
After one cell division,
the DNA was half as heavy,
so half of the DNA molecule contained heavy nitrogen
and the other half didn't.
This is not in line with the conservative DNA replication model,
which would predict that one molecule
would be all light and the other all heavy.
However, this is in line with the semiconservative
or the dispersive model.
After two cell divisions,
the DNA molecule was now either half heavy and half light
or entirely light.
So, this is now not in line with the dispersive model,
which would predict that the DNA after two cell divisions
would contain a mixture of heavy and light DNA.
Instead, this experiment agrees
with the semiconservative DNA replication model.
Every cell gets one old DNA strand
and one new one.
By discovering that two strands of DNA can separate
and provide the template for the production of two new strands,
Meselson and Stahl revolutionized genetics.
Scientists were very skeptical that this was even possible,
but Meselson and Stahl proved it
with a beautifully designed experiment.
They also went on to show that
heating DNA can cause the DNA strands to separate.
This simple concept is the basis
for an important technique we frequently use in the laboratory
called polymerase chain reaction,
which is used in genetic testing, forensics, and paternity tests.
Meselson and Stahl identified the fundamental process
by which our DNA gets passed on from cell to cell.
This is the basis for inheritance
and an essential part of our development
from a single cell to a complete organism
that maintains the same DNA sequence
in all of its cells.
This exciting finding
opened up many new doors and research avenues.
Because DNA is the command center of the cell,
we could now study how DNA gives orders
for the cell to follow.
What controls the ability of DNA to make protein?
How does one cell know it's a heart cell
and another cell know it's a liver cell,
if they all have the same DNA?
Now, DNA wasn't just a static double helix;
it was a molecule that was animated.
It could make more of itself.
It could instruct a cell to behave a certain way.
All of the secrets of biology were ready to be answered.
Today, we understand many of these questions.
We know that the process of DNA replication
is very complex,
with many proteins coming together to make this happen,
as well as proofreading and repair mechanisms
to make sure that DNA is properly copied.
We can even produce a heart cell from a skin cell.
We know what controls cell division,
and how we can stop or accelerate it.
We know what sorts of things can cause mutations, o
r changes in the DNA sequence,
and how that influences cell behavior,
such as in cancer.
It's amazing now to look back at this very fundamental finding
-- that DNA replicates in a semiconservative manner --
and see how it has revolutionized biology
and our appreciation for DNA.
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