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Sickle Cell Anemia


Debra L. Stamper
Harvard Medical School
Brigham & Women’s Hospital


In this case study on sickle cell anemia, students are introduced to some of the key researchers responsible for determining the molecular basis of the disease and learn about the functioning of erythrocytes as well as the notion that changes in the environment can influence the functioning of cells.  Students also become familiar with the process of osmosis and how it can influence the sickling of the erythrocytes.  Throughout the case, students must address experimental design questions. The case was designed for use in the first semester of an introductory majors biology course.


  • Identify pieces of experimental evidence.
  • Determine whether one piece of experimental evidence supports another piece.
  • Determine the need for "blind" tests.
  • Understand the proper use of a control for an experiment.
  • Recognize how the side groups of amino acids can influence the overall charge of a protein.
  • Recognize the interdependence of the different levels of protein structure.
  • Understand the role of the nucleus and plasma membrane in the normal functioning of a cell.
  • Recognize that changing the environment in a cell can alter the functioning of the cell.
  • Determine the osmolarity and tonicity of different solutions.
  • Predict the movement of water when cells are placed into solutions of different tonicity.
  • Understand how the process of osmosis can alter the concentration of intracellular molecules.
  • Understand that more than one variable may affect the sickling rate of red blood cells.
  • Predict possible side-effects of treating a patient with solutions of different tonicity.


Sickle cell anemia; thalassemia; thalassemic disorders; hemoglobin; red blood cell; amin acid; protein structure; osmosis; osmolarity; osmosis; tonicity; experimental design; Linus Pauling; Vernon Ingram

Topical Areas

Scientific method, History of science

Educational Level

High school, Undergraduate lower division



Type / Methods




Subject Headings

Biology (General)  |   Biochemistry  |   Cell Biology  |   Molecular Biology  |   Medicine (General)  |  

Date Posted


Teaching Notes

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Teaching notes are intended to help teachers select and adopt a case. They typically include a summary of the case, teaching objectives, information about the intended audience, details about how the case may be taught, and a list of references and resources.

Supplemental Materials

The supplemental materials below may be used with this case study. Many of them are tied to the HHMI short film "The Making of the Fittest: Natural Selection in Humans."  This film can be accessed from under the Videos tab above or directly at the following URL:

  Activity: How Do Fibers Form? hhmi/
  Activity: Mendelian Genetics, Probability, Pedigree, and Chi-Square Statistics hhmi/
  Activity: A Lesson on the Nature of Science hhmi/
  Activity: Testing a Hypothesis hhmi/

Answer Key

Answer keys for the cases in our collection are password-protected and access to them is limited to paid subscribed instructors. To become a paid subscriber, begin the process by registering.


The following video(s) are recommended for use in association with this case study.

  • Short Film: The Making of the Fittest: Natural Selection in Humans hhmi/
    A keenly observant young man named Tony Allison, working in East Africa in the 1950s, first noticed the connection and assembled the pieces of the puzzle. His story stands as the first and one of the best understood examples of natural selection, where the selective agent, adaptive mutation, and molecule involved are known - and this is in humans to boot. The protection against malaria by the sickle-cell mutation shows how evolution does not necessarily result in the best solution imaginable but proceeds by whatever means are available. Produced by HHMI BioInteractive. Running time: 14:03 min.
  • Film Guide: The Making of the Fittest: Natural Selection in Humans hhmi/
    This guide and quiz support the short film "The Making of the Fittest: Natural Selection in Humans." The "At a Glance Film Guide" provides a short summary of the film, along with key concepts and ties to selected curricula and textbooks. The "In-Depth Film Guide for Teachers" includes a more detailed summary and background information, discussion points, lists of related resources and references, and answers to the accompanying student quiz. The "Quiz" is designed as a summative assessment that probes student understanding of the key concepts addressed in the film. Produced by HHMI BioInteractive.
  • Animation: Sickle Cell Anemia hhmi/
    A one-minute animation about sickle cell anemia, a genetic disease that affects hemoglobin. A single nucleotide change in the hemoglobin gene causes an amino acid substitution in the hemoglobin protein from glutamic acid to valine. The resulting proteins stick together to form long fibers and distort the shape of the red blood cells. Produced by HHMI BioInteractive. Running time: 1:00 min.


Carol Bach, M.D.
Science Department
Palmer High School
Colorado Springs, CO
We used the case as an example of the scientific process with our freshmen Middle Years Programme International Baccalaureate (MYP/IB) biology students. It worked very well and the students enjoyed the step-by-step process. We used sections A, B, C. We also showed a DNA video that had a discussion of sickle cell disease. It was very effective. The case provides an excellent transition from the study of DNA and biotechnology to the study of genetics.

Kenneth R. Bridges, M.D.
Joint Center for Sickle Cell and Thalassemic Disorders / Department of Hematology
Brigham and Women's Hospital
Boston, MA 02115
Your cases are excellent in their depth and teaching quality. I had the good fortune to meet both Drs. Pauling and Castle. They did indeed have the famous conversation while traveling by train from a meeting. The other interesting historical item I recently learned came from Vernon Ingram. He did not come to the MRC with the intent of working on sickle hemoglobin. Another researcher had failed in some crystallography work on sickle hemoglobin because of the low resolution at the time. Ingram helped Max Perutz with putting mercury residues on hemoglobin A to improve the crystallographic resolution. Francis Crick then suggested that he look into the question of the difference between normal and sickle hemoglobin, since there was a left-over sample from the failed experiment. Science proceeds in the strangest ways!