Friedrich Miescher
• Began working with white blood cells in
1869.
• White blood cells are a major
component of pus in infections. As a
result, Miescher collected a lot of pus
from bandages at a local hospital.
• Added a weak alkaline solution to the
white blood cells– when he did the cells
decomposed and caused the nuclei to
move out of the solution.
• From the nuclei, Miescher isolated a
substance known as “nuclein”
• After chemical analysis, nuclein was later
renamed as DNA.
Frederick Griffith
• In the 1920s he was trying to develop a
vaccine for pneumonia.
• Began to wonder if a strain of bacteria
could transform into another strain.
• He took two strands of pneumococcus
bacteria (deadly strain [III-S] and nondeadly strain [II-R]) and injected them into
healthy mice.
• Firstly, he found that when injected with
the deadly strain (III-S) the mice died, and
when injected with the non-deadly strain
(II-R), the mice survived.
Frederick Griffith
• Secondly, he heated up the deadly
strain (III-S) to kill the bacteria and
when injected into the mice, they
did not die.
• Lastly, he co-injected the heated deadly
strain (III-S) with the non-deadly strain (IIR) and when injected into the mice, they
died.
• He concluded that some “principle”
transformed the non-deadly strain (II-R)
into a deadly strain (III-S).
• He called this the “transforming principle”
“Transforming Principle”
Rough strain: II-R
(non-deadly strain)
Smooth strain: III-S
(deadly strain)
Third Experiment
First Experiment Second Experiment
..
Joachim Hammerling
• In the 1930s, began experimenting with
Acetabularia, a form of green algae.
Cap
• He found that when you removed the cap, it
grew back, but if you removed the foot, it
would not grow back.
Stalk
• This showed that the instructions for
making the cap were in the foot (which
was where the nucleus was).
• He concluded that the nucleus contained
DNA, and was responsible for
development.
Foot
Oswald Avery, Maclyn McCarty and
Colin McLeod (1944)
• Was interested in the work that
Frederick Griffith did.
• What was the “principle” that
transformed the non-deadly strain (II-R)
into a deadly strain (III-S).
• They discovered that it was DNA,
not protein that was responsible for
transformation.
Erwin Chargaff
• In 1949, he began experimenting with
DNA.
• He isolated DNA from different
organisms and measured the levels of
adenine, guanine, thymine and cytosine.
These were his results:
DNA
Source
Adenine Thymine Guanine Cytosine
Calf
Thymus
1.7
1.6
1.2
1.0
Beef
Spleen
1.6
1.5
1.3
1.0
Yeast
1.8
1.9
1.0
1.0
Tubercle
Bacillus
1.1
1.0
2.6
2.4
Chargaff’s Rule
• Levene’s tetranucleotide theory stated
that adenine, guanine, cytosine, and
thymine would equal each other.
• However, Chargaff concluded that the
nucleotides must be arranged in a way
that adenine and thymine are equal
and that cytosine and guanine are
equal (A=T/C=G).
DNA
Source
Adenine
Thymine
Guanine
Cytosine
Calf
Thymus
1.7
1.6
1.2
1.0
Beef Spleen
1.6
1.5
1.3
1.0
Yeast
1.8
1.9
1.0
1.0
Tubercle
Bacillus
1.1
1.0
2.6
2.4
DNA Structure Was Discovered
• Through the work of
Miescher, Griffith,
Hammerling, Avery,
McCarty, McLeod and
Chargaff, the structure of
the nucleotide was
discovered.
• The structure of the
nucleotide included:
pentose sugar attached
to a phosphate group at
carbon 5 and a
nitrogenous base at
carbon 1.
Alfred Hershey and Martha
Chase
• Conducted an experiment in 1952 on
bacteriophage (viruses that attack and
infect bacteria).
• Using radioactive isotopes, Hershey
and Chase traced the movement of
DNA and protein during phage
infection.
• They showed that DNA, not protein
entered the bacterial cell during
phage reproduction and that only
DNA was passed on to phage
offspring.
• This concluded that DNA, not
protein carries the genetic material of
the cell.
Rosalind Franklin
• Began researching the structure of
DNA in the early 1950s.
• Franklin used X-ray diffraction (a
technique used to examine the shape
and structure of a molecule) to take a
picture of a DNA molecule.
• The picture showed the double
helical structure of DNA. However,
the picture shows the DNA molecule
from the end, not the side.
James Watson, Francis Crick and
Maurice Wilkins (1953)
• Wilkins passed on the photo
that Franklin had taken to
Watson and Crick.
• Using Franklin’s photo and
Chargaff’s rule, Watson and
Crick were able to explain and
prove the double helical
structure of DNA.
• Using Chargaff’s data, they were
able to come up with the
“complementary base pairing” in
DNA where a purine (A/G) always
binds with a pyrimidine (T/C).
James Watson, Francis Crick and
Maurice Wilkins (1953)
• They proposed that the helix in
DNA turned clockwise and was
a right handed helix.
• They concluded that the helix
would make a complete turn
every 10 nucleotides, which is a
distance of 3.4nm, so the space
between nucleotides is 0.34nm.
• Also they discovered that DNA
strands run anti-parallel to each
other (one strand runs in a 5’ to 3’
direction and the other strand runs
3’ to 5’.)
James Watson, Francis Crick and
Maurice Wilkins (1953)
• For all their research,
Watson, Crick and
Wilkins won the Noble
Peace Prize in 1962.
• Rosalind Franklin
was never given any
credit for her
discovery, and died
in 1958.