Modeling Infection

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Students will explain how viruses infect cells using the Hershey-Chase experiment.

Big Idea

Understanding the life cycle of a model organism helps us understand how many viruses reproduce.

What Students Will Learn in This Lesson

1 minutes

In this lesson, student use the classic Hershey-Chase experiment to better understand how viruses infect cells. By beginning with culturing bacteriophages, students gain an appreciation of how hard it is to culture these viruses.  Next students read about the Hershey-Chase experiment to see if they can develop a model of how bacteriophages infect the bacteria cell from the results of this experiment. Here is an overview of what students will learn today.  


5 minutes

To introduce viral infection, have students watch I'm a Virus. (My students watch from 0:00-2:25). 

Explain to students that we will be looking at a study that provided the information for this model. 

Then ask students to consider the following scenario.

Have you ever been sick with a head cold? People have different ideas about what causes a cold. List the things that cause you to “catch a cold” in your lab notebooks.  

Can you catch a cold from

  • having a fever
  • being wet
  • being wet and cold
  • germs
  • spoiled food
  • not getting enough sleep
  • lack of exercise
  • cold weather
  • dry air
  • imbalance of body fluids 


Explain your thinking. Describe how people “catch a cold.” 

Adapted from Keeley and Tugel. 2009. “Catching a Cold” Uncovering Students Ideas in Science: 25 New Formative Assessments.

Student Activity: Culturing Bacteriophages

20 minutes

Student groups will perform a serial dilution and plate bacteriophages.  Refer to the handout, Lab Techniques in Microbiology: Culturing Bacteriophages, for complete list of instructions for this protocol.  (Here are protocols for making hard (1.5%) agar and soft (0.7%) agar as well.)

This is a list of necessary cultures, media, and disposable lab ware. All disposable materials are enough for one group of students.

  • Disposable container of sewage (sample of sewage containing bacteria and virus will last for days, possibly weeks, at room temperature; refrigerated samples will last for months. But do not store in a refrigerator that is used for food)

  • Erlenmeyer flask (125 or 250 mL)

  • 5 mL of 10X nutrient broth

  • Nutrient broth culture of E. coli strain B (or K12)

  • Two or three tubes of sterile nutrient broth (5 mL each)

  • Sterile pipettes (1 or 5 mL; disposable ones are suitable)

  • Bench top centrifuge (1000 to 2500 rpms)

  • 12 or more sterile disposable centrifuge tubes (15 or 50 mL are suitable)

  • Package of sterile membrane filters (0.45 μm pore size or smaller)

  • Forceps

  • Bunsen burner or alcohol burner

  • Sterile side arm Erlenmeyer flask and filter setup, with an aspirator or vacuum pump; alternatively, syringe filtration can be used

  • 10 or more tubes (5 mL each) of sterile soft nutrient agar (0.7 percent nutrient agar) kept liquid in 50°C water bath

  • 12 or more petri plates of solid nutrient agar, 15 mL per plate (can be purchased)

  • 37°C incubator, if available 

    Cultures are incubated overnight and evaluated the next day.

     (Note: I like to have students complete this activity to help them understand how bacteriophages are cultured. Even though, it requires a lot of preparation outside of class, it is worth the time. Students are able to view the results the following day. For an introductory class like biology, I prepare the effluent, autoclave all the glassware, and prepare the agars and nutrient broth ahead of time. If using this protocol with a more advanced course, this protocol could be modified with students preparing their own agar and nutrient broth as well as wrapping and autoclaving their own glassware.)

    This protocol is based on Bunyard, Britt. 2000. "Viral Investigation: Students learn to isolate a common, nonpathogenic virus." The Science Teacher.  9:38-41.

Student Activity: Reading Primary Sources

15 minutes

Provide students with a copy of the modified write-up of the Hershey-Chase experiment based on Hershey and Chase's article or the original article depending on the student's reading ability. Students also receive a copy of a scaffolding worksheet

Allow students a chance to read and highlight the important points of the research as directed by the scaffolding worksheet. Another option would be to pair students up with their clock buddies and have them read the worksheet together. See my teacher reflection for more information on this strategy.

(Note:  My biology class is a sophomore level class. For students that can read at a college reading level, I give them the original journal article. Those students that can read at grade level, receive a slightly modified handout. I write these reading guides myself based on the original article, then I check readability using an online readability calculator.  To find out more about how I do this check out my teacher reflection.) 

All student worksheets are based on Hershey, A. D. and Chase, M. 1952. Independent functions of viral proteins and nucleic acid growth in bacteriophageJournal of General Physiology. 36:39-56.





Question and Answer: Interpreting the Results of the Hershey-Chase Experiment

15 minutes

Poll the class after students have read the primary source. Do they think protein or DNA is the genetic material? Have them give their responses by signing a p or d close to their body or writing their responses on a sticky note and holding it up.

Then give them the following background. In 1952, Alfred Hershey and Martha Chase designed experiments to find out whether protein or DNA provides genetic information.  Hershey and Chase labeled the DNA of bacteriophages with a phosphorus isotope and the protein in the capsid with a sulfur isotope.  The bacteriophages were allowed to infect the bacteria E. coli

Present the findings of the study to students.  Summary of findings:  

  • At least 80 percent of the sulfur-containing proteins stayed on the surface of the host cell.
  • Most of the viral DNA entered the host cell upon infection.
  • After replication inside the host cell, 30 percent or more of the copies of phage virus contained radioactive phosphorus.

Then ask

  • Do the results of these experiments support the idea that proteins are the genetic material or DNA is the genetic material?  Provide evidence to support your argument. 
  • If proteins and DNA had entered the cell, would these data be useful to answer Hershey and Chase's question?  

Here are examples of completed student work:  Student Work Sample Modified for At Grade Level Reading and Scaffolding Worksheet-Modeling Infection student work sample.  

Putting It All Together: What do the Results Mean?

5 minutes

Revisit the scenario presented at the beginning of class. Ask students which of the items explain the causes of the common cold, how the common cold is transmitted, what contributes to weakened immune system that has trouble fighting off a virus, and physiological response to an infection. Have students write causes, transmission, weakened immune system, or physiological response next to the items.  Then discuss why the best answer is germs?

Ask students, in light of the findings from the Hershey/Chase experiment,  how could you explain how individual caught a cold.

Have students record their responses in their lab notebook.  


For homework, students will watch a flipped lecture that explains the lysogenic and lytic cycle of viral replication in more detail.  They will respond to a Google form to indicate they have watched the lecture. (Read more about my rationale for having a flipped classroom here.)