NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

Putting the Pieces Together:

The Discovery of DNA
Structure and Replication
by
Kevin M. Bonney
Liberal Studies, Faculty of Arts and Sciences
New York University, New York, NY

Part I – Setting the Stage

In the autumn of 1952, while the weather in London, England, was cooling down, the race to discover the structure of
DNA was heating up inside two rival laboratories: the Cavendish Lab at Cambridge University and the laboratory of
J.T. Randall at nearby King’s College. DNA had recently been identifed as the hereditary material that organisms use
to transmit genetic traits from one generation to another. Tis fnding is largely attributed to the work of two groups
of American scientists, Oswald Avery, Colin MacLeod, and Macyln McCarty of the Rockefeller Institute, and Alfred
Hershey and Martha Chase of Cold Spring Harbor Laboratory, though many important experiments conducted by
other scientists were crucial to developing this understanding. Te next great challenge was to identify the structure of
DNA so that we could understand how the information contained in DNA is copied and passed from cell to cell, and
how that information is translated into the instructions for building the proteins necessary for life.
Te groundbreaking research of the Cavendish and Randall laboratories describing the structure of DNA was
published in a series of papers in the journal Nature on April 25, 1953 [Wilkins et al., 1953; Franklin et al., 1953].
Tese would become known as some of the most important scientifc papers ever published, as well as a symbol of
great controversy involving allegations of misogyny and ethics violations among scientists who would go on to win a
Nobel Prize.

Preparing for Your Mission

It’s now your job to fgure out the next piece of the puzzle: How do cells make new copies of their DNA? Before you
can fgure out how DNA is replicated, you must understand the structure of DNA. To prepare for your task, answer
the following questions to assess your understanding of DNA structure on your own, without using any outside
sources. You will then be asked to view a video.

Questions
1. Te structure of DNA is a:
A. alpha helix
B. single helix
C. double helix
D. triple helix
2. DNA is made of repeating units called:
A. amino acids
B. monosaccharides
C. nucleotides
D. peptides

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3. Te “D” in DNA stands for:

A. Darwin
B. Deoxyribose
C. Dimethyl
D. Dinucleic acid
4. Te bonds that hold the backbone of each strand of DNA together are called:
A. hydrogen bonds
B. ionic bonds
C. peptide bonds
D. phosphodiester bonds
5. Te information contained in DNA is encoded by the:
A. hydrogen bonds on the inside of the DNA molecule
B. nitrogenous bases on the inside of the DNA molecule
C. phosphate groups on the outside of the DNA molecule
D. sugars on the outside of the DNA molecule
6. In which direction is DNA read?
A. 0' to 1'
B. 1' to 3'
C. 3' to 5'
D. 5' to 3'
7. Te letters in the genetic code of DNA are A, C, G, and T. Te A stands for:
A. amino
B. adenine
C. alanine
D. aspartame
8. If one strand of DNA is AGCTA, the complementary strand would be:
A. AGCTA
B. ATCGA
C. CTAGC
D. TCGAT
Whether you are a DNA novice or a pro, watching the following video should help you put the pieces together. After
watching the video, answer the questions again to demonstrate what you know now. You may wish to watch the video
more than once before moving on to the questions.
Te Chemical Structure of DNA
http://www.hhmi.org/biointeractive/chemical-structure-dna

References
Franklin, R.E. and Gosling, R.G. 1953. Molecular confguration in sodium thymonucleate. Nature 171(4356):740–1.
Howard Hughes Medical Institute. Te Chemical Structure of DNA. http://www.hhmi.org/biointeractive/chemical-
structure-dna.
Wilkins, M.H., et al. 1953. Molecular structure of deoxypentose nucleic acids. Nature 171(4356):738–40.

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Part II – Discovering the Structure of DNA

Te story of how DNA structure was discovered is not only one of the most important tales in the history of science, it
is also the root of a great controversy that will live on for many years. It is your job to research the collaborations and
controversies that made the discovery of DNA structure possible, and determine once and for all who deserves the credit
for this groundbreaking feat of science. Te main characters in the story are named Francis Crick, Rosalind Franklin,
James Watson, and Maurice Wilkins. To understand this story, read Watson and Crick’s original scientifc paper:
Watson, J.D. and Crick, F.H. (1953) Molecular structure of nucleic acids; a structure for deoxyribose
nucleic acid. Nature. 1953 Apr 25;171(4356):737-8. http://www.nature.com/nature/journal/v171/n4356/
pdf/171737a0.pdf.
After you have read Watson and Crick’s paper, watch this short video to strengthen your understanding of the
implications of that work:
Te Secret of Life—Discovery of DNA Structure. Produced by Virginia Commonwealth University. Running time:
8:36 min. Date: 2014. http://youtu.be/JjO6n85wq8A.
You may also wish to access the following resource for more information:
Te structure of DNA: Cooperation and competition. Understanding Science Team. Te University of California,
Berkeley website. http://undsci.berkeley.edu/article/dna_01.
With the help of your peers, analyze, evaluate, and debate some of the important ethical implications of the work
conducted by Crick, Franklin, Watson, and Wilkins.

Questions
1. Why is understanding the structure of DNA and how it is replicated important? List some technologies and
practical applications that could not have been developed without this understanding.
2. How does the structure of DNA identifed by Watson and Crick difer from the model previously proposed by
Linus Pauling and others?
3. What discovery by Erwin Chargaf helped Watson and Crick build their model of DNA structure? How was
this piece of information helpful to them?
4. What is the main scientifc weakness you notice in Watson and Crick’s paper?
5. Te conclusion of the paper published by Watson and Crick includes the now rather famous statement: “It has
not escaped our notice that the specifc pairing we have postulated immediately suggests a possible copying
mechanism for the genetic material.” Describe what this statement means and why it is signifcant.
6. Describe the specifc contribution of each of the following researchers to the discovery of DNA structure:
• Francis Crick
• Rosalind Franklin
• James Watson
• Maurice Wilkins
7. In their paper, how do Watson and Crick acknowledge Rosalind Franklin for her contribution to their work ?
8. Is Watson and Crick’s acknowledgement of Franklin satisfactory, or did she deserve more credit? Your instructor
will divide you into two groups to debate this question.
• If you are in the Watson and Crick group, write a one-paragraph argument from their perspective. Defend the
way you have treated Rosalind Franklin and provide an argument that you have given her all of the credit
she deserves. Support your claims using information from the paper and video you just watched. Prepare to
debate your position with members of the other group.

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• If you are in the Franklin group, write a one-paragraph argument from your perspective. Defend yourself
against the treatment you received from Watson and Crick, and argue why you deserve more credit for the
discovery of DNA structure than you have been given. Support your claims using information from the paper
and video you just watched. Prepare to debate your position with members of the other group.

1. It's the blueprint for all life on the planet. Allows us to comprehend flaws and allows beings and things to defend
themselves against sickness. Because if DNA is never replicated, meiosis and mitosis would gradually halve the
size of the genome until each cell dies, understanding replication is critical.

2. The Linus Pauling model had triple helix with the phosphate backbone on the inside and the nucleotides on the
outside. while the Watson-Crick model had the phosphate backbone on the outside with the nucleotides in the
middle.

3. He discovered that the units of adenine and thymine are equal to each other and that the units for cytosine and
guanine are also equal to one another. it allowed them to know what percentage of each nucleotide makes up a
particular section of DNA.

4. This paper lacks a statical analysis of their findings, as well as a general structure, by today's scientific standards.
There is no p-value, and their background study is primarily critical of other scientists' past work.

5. This statement relates to DNA's ability to break into two pieces and use one of them as a template for replication.
This is significant because it is the base on which cells code for proteins; without the ability to replicate, cells would
be unable to translate and transcribe information. Essentially, the whole thing is a waste of time.

6. Francis Crick: contributed to the invention of the helical diffraction theory, which aided in the understanding of DNA
structure; he also collaborated with James Watson in the discovery of DNA's double helix structure. He also proved that a
sequence of three nucleotide bases on a single DNA strand codes for a single amino acid.
Rosalind Franklin: using the x-ray diffraction created images of DNA, which was later used by Watson and Crick to determine
the structure of DNA.
James Watson: He helped deduce the structure of dna, along with Crick.
Maurice Wilkins: it was his idea to use X-ray crystallographic techniques to study DNA.

7. They mention that they were stimulated by the unpublished results of Dr. Wilkins and Dr. Franklin's lab.

8. First and foremost, we appreciate you for your important contribution to molecular biology. I
developed this argument to address the elements in your paper that I considered to be inappropriate
for work ethics. As Rosalind Franklin, I believe I made a greater contribution to the discovery of the
double-helix structure of deoxyribonucleic acid than you acknowledged in your scientific work. Giving
greater credit to Astbury for clearing the air with X-ray diffraction but not to me was, in my opinion, an
unpleasant approach.

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Part III – Building a Model of DNA Replication

Now that you can illustrate the structure of DNA and describe the experiments and ethical issues related to its
discovery, you are prepared for your mission: To determine how cells make new copies of their DNA.
Remember, it is still the 1950s. At this time, three hypothetical models have been proposed to explain how DNA is
replicated. Tese models, known as the conservative model, the dispersive model, and the semi-conservative model,
are illustrated in Figure 1.

Figure 1. Hypothetical models of DNA replication.

In the conservative model, both original template DNA strands form one double helix after replication, while the
two newly synthesized strands form a second double helix. In the dispersive model, the template DNA is broken into
double-stranded segments that act as templates for the synthesis of new double helix molecules; the two resulting
double helix molecules each contain half of the original template DNA and half of the newly synthesized DNA. In
the semi-conservative model, the original DNA strands are separated, and each acts as a template for the synthesis of a
new strand of DNA to complete the double helix.
To fgure out which model of DNA replication correctly illustrates how living organisms make new copies of their
DNA, you must frst fnd a way to distinguish the newly synthesized DNA from the original template DNA. Next,
you want to fgure out what would happen in each model and compare that to the actual experimental data.
Step 1. To start, make a double-stranded DNA molecule to represent the original template DNA. Make each strand
of the molecule six nucleotides long, using gumdrops to represent the nucleotides of the original template
DNA. Use toothpicks to form bonds that connect the gumdrops in each strand and hold the two strands
together.
Step 2. Choose one model of replication (conservative, dispersive, or semi-conservative) as the mechanism for
copying your DNA molecule. From now on use marshmallows to represent newly synthesized DNA and

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toothpicks to form bonds. Make a copy of the original template DNA molecule by following the principles
of the model of replication that you chose.
Step 3. Repeat Steps 1 and 2 for the other two models of DNA replication.
Step 4. Record the percentage of gumdrops and marshmallows in each DNA molecule using the table below.
(Divide the number of each by the total number of both and multiply by 100 to calculate the percent.)

After one round of replication:

Model DNA molecule A DNA molecule B

100
________% gumdrops ________% gumdrops
Conservative
________ % marshmallows 100
________ % marshmallows

50
________% gumdrops 50
________% gumdrops
Dispersive
50
________ % marshmallows 50
________ % marshmallows

50
________% gumdrops 50
________% gumdrops
Semi-Conservative
50
________ % marshmallows 50
________ % marshmallows

Step 5. Using only marshmallows and toothpicks, make a copy of each DNA molecule you have from Step 3
following the principles of the three models of replication.
Step 6. Record the percentage of gumdrops and marshmallows in each DNA molecule in the table below. (Divide
the number of each by the total number of both and multiply by 100 to calculate the percent.)

After two rounds of replication:

Model DNA molecule A DNA molecule B DNA molecule C DNA molecule D

100
______% gumdrops 100
______% gumdrops ______% gumdrops ______% gumdrops
Conservative
______ % marshmallows ______ % marshmallows ______
100 % marshmallows ______
100 % marshmallows

50
______% gumdrops 50
______% gumdrops 50
______% gumdrops 50
______% gumdrops
Dispersive
50 % marshmallows ______
______ 50 % marshmallows ______
50 % marshmallows ______
50 % marshmallows

______%
50 gumdrops ______% gumdrops ______%
50 gumdrops ______% gumdrops
Semi-
Conservative
50 % marshmallows ______
______ 100 % marshmallows ______
50 % marshmallows ______
100 % marshmallows

Questions
1. Describe what occurs in each of the following models of DNA replication: conservative, dispersive, and semi-
conservative.
2. Describe how each model of DNA replication difers in terms of the observations you made using gumdrops
and marshmallows. How can you tell each model apart based on the relative amount of gumdrops and
marshmallows in each DNA molecule?

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Optional Exercise
A short video entitled Building a Model of DNA Replication demonstrating the activity above can be viewed at:
https://youtu.be/SAXHwkKe6Bc
After watching the video, answer the following questions:
1. Which of the following statements about the use of gumdrops and marshmallows in this activity is true?
A. Both are used to represent nucleotides.
B. Gumdrops represent nitrogen and marshmallows represent phosphorus.
C. Gumdrops represent DNA and marshmallows represent RNA.
D. Gumdrops represent nucleotides and marshmallows represent phosphodiester bonds.
2. In this activity, DNA molecules containing only original template DNA are represented using:
A. gumdrops and toothpicks only.
B. marshmallows and toothpicks only.
C. gumdrops and marshmallows only.
D. toothpicks only.
3. After one round of replication, what has been produced by the conservative model of replication?
A. One molecule that contains 0% gumdrops and 100% marshmallows, and one molecule that contains 100%
gumdrops and 0% marshmallows.
B. Two molecules that contain 100% marshmallows and 0% gumdrops.
C. Two molecules that both contain 100% gumdrops and 0% marshmallows.
D. Two molecules that both contain 50% gumdrops and 50% marshmallows.
4. After two rounds of replication, which of the following is true of the four DNA molecules produced by the
semi-conservative model?
A. All four contain 25% gumdrops and 75% marshmallows.
B. All four contain 50% gumdrops and 50% marshmallows.
C. Two contain 50% gumdrops and 50% marshmallows, and two contain 0% gumdrops and 100% marshmallows.
D. Two contain 100% gumdrops and 0% marshmallows, and two contain 0% gumdrops and 100% marshmallows.
5. Which model(s) of DNA replication never produce(s) a DNA molecule that contains both gumdrops and
marshmallows?
A. Te conservative model only.
B. Te dispersive model only.
C. Both the conservative model and the dispersive model.
D. Both the dispersive and the semi-conservative model.
Questions
1. Conservative claimed that DNA didn't split open at all, but rather kept the parent strands intact while forming a new and distinct copy.
Dispersive- DNA only copied itself in small bits at a time, resulting in new strands that alternated parent and daughter DNA.
Semiconservative- this model would result in two new double strands of DNA, each one with one strand of parent DNA and one strand of
daughter DNA
2. ~In the conservative model, there would be either 100% gumdrop or 100% marshmallow. Meaning there would be dense DNA at the
bottom of the tube and less dense DNA at the top of the tube and nothing in the middle
~In the dispersal model, there would be 50% gumdrop and 50% marshmallow in each strand of DNA. Therefore, there would only be a
strip of DNA in the middle of the tube.

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Part IV—Testing the Model of DNA Replication

Now that you can describe what occurs in each of the three hypothetical models of DNA replication and identify
which type of replication has occurred by labeling the nucleotides of the original and newly synthesized DNA, you
are ready to complete your mission and determine which model of replication correctly explains how cells make new
copies of their DNA. However, because real DNA does not incorporate gumdrops or marshmallows, and is actually
too small to see with your eyes, you will want to use data collected by two other famous scientists, Matthew Meselson
and Franklin Stahl, to help you complete your mission.
To distinguish between newly replicated DNA and the original template DNA from which it was copied, Meselson
and Stahl used isotopes of nitrogen called 14N and 15N to label the nitrogenous bases of DNA. Isotopes of nitrogen
difer in the number of neutrons they contain; 15N, having one more neutron than 14N is denser than 14N, since
neutrons comprise much of the mass of atoms. Tus, DNA containing 15N can be distinguished from DNA
containing 14N by comparing the density of each DNA molecule. Tink of 14N as the marshmallows you used when
making your models, and 15N as the denser gumdrops.
Meselson and Stahl used Escherichia coli bacteria as a source of cells to study DNA replication. Te Escherichia coli
were frst grown in nutrient broth containing 15N as the only source of nitrogen until all of the nitrogen in the
bacteria’s DNA was 15N. Next, the bacteria were placed in media containing only 14N and allowed to divide, so the
newly synthesized DNA would use and incorporate the 14N into its structure.
During each division, the amount of DNA was doubled as one newly synthesized DNA molecule was made from each
template DNA molecule.
Meselson and Stahl knew that DNA containing 15N could be separated from DNA containing 14N by centrifuging
the DNA molecules in a density gradient, which causes molecules of higher density to move toward the bottom of
the gradient and molecules of lower density to move toward the top. Unlike the models you just made, Meselson and
Stahl could not see real DNA molecules with their eyes or even using a microscope. However, they knew that DNA
absorbs ultraviolet (UV) light, and that by shining UV light on the density gradients they made they could determine
where in the gradient the DNA was located because a shadow would be cast in the location where DNA was absorbing
the light.
Te data that Meselson and Stahl collected
in this way is represented in Figure 2.
Remember that the bacteria started out
with 15N comprising 100% of the nitrogen
in their DNA, then they were supplied
only 14N so that any newly synthesized
DNA would contain 14N.
Use the knowledge you gained from
building the three hypothetical models
of DNA replication with gumdrops and
marshmallows to complete your mission
by answering the following questions.

Questions
1. Before analyzing the results of this
experiment, Meselson and Stahl needed
to know where DNA containing 100%
14
N or 15N would be in the density
gradient. Predict what Meselson and Figure 2. Representation of data collected by Meselson and Stahl.
Stahl did to fgure this out.

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2. How can you interpret the data collected after one round of division? In other words, what do the number and
location of the band(s) present signify?
3. Which model(s) of DNA replication are consistent with the data collected after the frst round of replication?
Which model(s) can be ruled out? Why?
4. For any models of DNA replication that were ruled out after the frst round of replication, what would the data
have looked like if the DNA had, in fact, been replicated according to that model?
5. Which model of DNA replication is consistent with the data collected after the second round of replication?
Which model can be ruled out? Why?
6. What would the data have looked like if the DNA had, in fact, been replicated according to the model just
ruled out?
7. According to the model of DNA replication identifed as correct, what would the data look like after a third
round of a replication? How about after a fourth round?
8. Why are bacteria like Escherichia coli good for studying DNA replication (as opposed to using other types of
cells)?
1.They grew some DNA in 14N broth and some DNA in 15N broth
2.Their was half 14N DNA and half 15N DNA
3.Semiconservative and dispersal models are consistent with the data collected after the first round of replication.
In conservative, the DNA settled in a middle of the tube which rules out the conservative model since in the conservative
model, the DNA should be at the bottom or top of the tube, not the middle.
4.The DNA should have settled on the top of the tube or the bottom. 5.Semiconservative model is consistent with data
collected after second round of replication
The dispersal model can be ruled out because after the second round, there should’ve been DNA strip in the middle and at
the top but there was only a strip at the middle in the dispersal model
6.A strip of DNA in the middle only.
7.There would still be a small strip of 14/15N mixed DNA and the rest would all be at the top of the tube since it would be
the less dense 14N DNA.
8.Because of its simplicity and its rapid growth

•
Case copyright held by the National Center for Case Study Teaching in Science, University at Buffalo, State University of New York.
Originally published July 28, 2015. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.
Licensed photograph of scientist with DNA in title block ©Sergey Nivens | Fotolia, ID#59039425.

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