Case Teaching Notes for
“An End to Ulcers? A Case Study in the Scientific Method”

Introduction / Background

This case study is a “clicker case.” It combines the use of student personal response systems (clickers) with case teaching methods and formats. The case is presented in class using a series of PowerPoint slides punctuated by questions (called “clicker questions”) that students respond to before moving on to the next slide. In this way, students work their way through the material to understand (and solve) the problem presented in the case. Specifically designed for use in large introductory science classes, the method integrates lecture material, case storylines, student discussion, (clicker) questions, clarification of answers to those questions, more lecture, and data.

The case teaches students about the scientific method. Frequently the scientific method is taught in introductory undergraduate classrooms as a series of steps to be methodically followed that ultimately lead to advancement in scientific understanding. In reality, the acquisition of new scientific knowledge and the pragmatic application of the scientific method is a far richer and more dynamic process, often involving emotionally charged human interactions. Rarely do new scientific theories describe explanations for phenomena where no previous explanation has been offered in the past. Thus, in practice, the application of the scientific method frequently involves a struggle to replace a long-held dogma.

This case describes the Nobel Prize-winning discovery by two Australian biomedical scientists that human gastritis and peptic ulcer disease is most frequently due to a chronic bacterial infection of the stomach. Students have the opportunity to see how the researchers, Drs. J. Robin Warren and Barry J. Marshall, pursued an initial observation by applying the steps of the scientific method to validate their theory. In addition, students learn about the worldwide debate that ensued among medical scientists prior to an acceptance of this new theory.

Developed for a large introductory biology course, this case could be used as well in an undergraduate microbiology course for pre-nursing majors to introduce the contemporary theory that many chronic medical conditions have an infectious origin. Students are expected to have been exposed to the idea of the scientific method in high school. Since this case is most likely to be used at the beginning of the semester/course, no additional knowledge beyond high school biology and a review of appropriate pages in the course textbook is expected.

Objectives

• Construct a hypothesis based on reported observations.
• Develop a prediction based on a hypothesis.
• Identify appropriate methods (including controls) for testing a hypothesis.
• Examine data and draw conclusions about whether or not they support a hypothesis.
• Develop an understanding of how prevailing ideas in science are modified.
• Apply the scientific method using a real life situation.

Misconceptions

• Scientific research using the scientific method progresses in a linear fashion.
• Conclusions from clear experimental results are always accepted by the scientific community.
• Ulcers are caused by stress.

Classroom Management / Blocks of Analysis

As the class moves through the case there are opportunities for the instructor to clarify (through mini-lectures) several aspects of the scientific process including experimental design, hypothesis testing, and the role of alternative hypotheses; the importance of new/different technologies in allowing scientists to look at phenomena in new ways; experimental controls; and skepticism vs. dogma in science. These opportunities mostly come after a clicker question or set of clicker questions that test students’ knowledge and ability to apply concepts.

In addition, throughout the case there are times when students are asked to discuss with their neighbors in small groups the design of experiments and graphing of predicted results. Instructors need to budget time accordingly in the class period for these discussions. Depending on the background of the students and the duration of the class, these discussion breaks may take anywhere from 2–10 minutes.

In-Class Case Presentation

Introduction (Slides 1–10)

The case begins with a question (Slide 2) intended to assess the students’ initial understanding of the cause of stomach ulcers. There is no “correct” answer.

The next slide, Slide 3, provides a historical overview of our understanding of stomach function and ailments. The following introductory information can be used by the instructor while showing Slide 3 to help students understand the scientific community’s interpretation of the stomach and stomach ailments, and leads to the initial hypothesis for the cause of ulcers—the “excess acid hypothesis.”

One of the first systematic studies of the human stomach was done by Dr. William Beaumont, a physician at an army post in the 1800s. Alexis St. Martin, a fur trapper who was shot accidentally, ended up as Beaumont’s patient. St. Martin survived, but one of his wounds healed with an opening to the outside of his body (fistula) that allowed Beaumont to peer directly (or pass a piece of food) into the stomach. St. Martin allowed Beaumont to observe the workings of his stomach and conduct experiments on stomach digestion. Beaumont was the first physician to describe the acidic environment of the stomach, and the relationship between acid levels and moods in his patient.

Humans have probably suffered from stomach ulcers for all of their history. The ancient Greeks recognized the symptoms of stomach ulcers: a burning or gnawing pain in the abdomen that may or may not follow a meal. The pain may be severe and frequent enough to awaken the sufferer at night. These stomach pains may last for several weeks, and be followed by several pain-free weeks. One of the earliest remedies for ulcers is recorded by the Greek physician Hippocrates, who treated people by having them eat crushed clamshells to relieve the symptoms.

During the 20^th century, physicians’ understandings of stomach ailments increased. Doctors defined gastritis as an inflammation of the stomach lining (white blood cells present), and peptic ulcers as an erosion of the lining of the stomach. Gastritis and ulcers are highly correlated, as are gastric ulcers and stomach cancer. Stomach cancer is the second most common cancer worldwide, and in the developing world is still a major cause of death.

Most doctors in the 20^th century understood that stomach ulcers resulted from age, stress, diet, and drinking too much alcohol. Several scientists proposed that these factors resulted in excess acid in the stomach (normal stomach pH = 2–3). They suggested excess acid in the stomach caused inflammation and erosion of the stomach lining (“excess acid hypothesis”). The most common treatments for gastritis and ulcers were: drinking lots of milk, adopting a diet of bland foods, making lifestyle changes to decrease stress, and, in the worst cases, surgery to remove the ulcer. These treatments helped control symptoms, but once someone had stomach ulcers they usually recurred over her or his lifetime.

Slide 4 asks students to discuss with their neighbors an experimental test of the excess acid hypothesis. This can take as little as 2–3 minutes or up to 10 minutes depending on the instructor and the length of the class period. Many of my students already have some familiarity with experimental design, so I usually give them 2–3 minutes to talk to their neighbor, then may ask for some examples from the class without commenting on their designs.

Slide 5 asks students to evaluate several possible experimental designs. Upon completion of this question, the instructor can point out the pluses and minuses of the tests listed.

Slide 6 asks students to determine what step in the scientific method is represented by their plan.

Slide 7 describes a possible study design in which doctors divide patients into two groups: one group of patients receives antacids while the other receives a placebo.

Students should be directed to discuss with 2 or 3 other students what they predict the results would look like if the excess acid theory were supported by the results of this study and to draw a graph (see Slide 8). Depending on the abilities of the students, the instructor may need to go over the parts of the graph—what the axes represent and that their prediction should come in the form of a bar graph with one bar per treatment group.

Slide 9 is designed to test the students’ ability to predict the results that would support a given hypothesis.

Using Slide 10, the instructor should explain that this type of controlled experiment was NOT conducted. However, a common observation of physicians at the time was that patients who took drugs or antacids to lower stomach acid levels had a decrease in their ulcer symptoms. If the patients stopped taking the drugs or antacids, their ulcers would return.

New Observations (Slides 11–29)

With Slide 11, the instructor can explain the following:

In 1979, Dr. J. Robin Warren was a pathologist working at the Royal Perth Hospital in Western Australia. As a regular part of his job, he examined stomach biopsies of patients admitted for various stomach ailments. Pathologists like Dr. Warren pride themselves on their ability to diagnose cancer and other issues quickly by looking at tissue under the low power of a microscope. However, Dr. Warren, unlike his colleagues, would often also look under higher power lenses at the tissue samples he was sent. Looking under higher power allowed him to see things that were not visible under low power. As a result, he noticed some unusual characteristics in the stomach biopsy samples of ulcer patients.

The question in Slide 12 illustrates that many of the things that scientists study are not totally new to science, but a new way of looking at things can reveal new explanations for natural phenomena. This is an important message for the instructor to convey upon completion of this question. New and different technologies (or as in the case of Dr. Warren, just looking at things in a new way—a little more closely) allow scientists to reexamine their explanations for natural phenomena. Often these new ways of looking at things reveal important patterns that were not apparent before, and provide new explanations for commonly observed phenomena.

Dr. Warren identified the smudges he saw as bacteria, but his colleagues did not believe there were bacteria in the stomach (Slide 13).

Slide 14 asks students to use previous knowledge (and information from the introduction to the case) to make conclusions. It also illustrates how scientists with assumptions about what is the “correct” explanation for a phenomenon may not be open to new explanations/observations, and how scientists must balance skepticism and dogmatism—an important point for the instructor to make at the completion of this question.

As described in Slide 15, after Dr. Warren used a special stain that highlights bacteria on his slides and showed his colleagues the slides under the high power of the microscopes, he convinced them that bacteria were present on his slides. However, though Dr. Warren had convinced his colleagues in Perth that the bacteria were really on the slides, they still did not believe that the bacteria were important in causing ulcers.

Slide 16: The instructor asks the students to come up with some other explanations for why bacteria were appearing in Dr. Warren’s slides. Again, depending on the time in the class period, the instructor’s desires and the background of the students in the class, this activity can take anywhere from 2–7 minutes.

Slide 17: Some of the alternative explanations (hypotheses) that Dr. Warren’s colleagues suggested were:

1. The bacteria on the slides represent contamination of the biopsy specimens that took place AFTER samples were taken from the patients.
2. The bacteria are a species that lives in the stomach as a commensal (doing no damage).
3. The bacteria are an opportunistic species that arrives AFTER ulcers have already weakened the stomach’s defenses.

At this point, the instructor can give a mini-lecture on skepticism versus dogma in science and the important role that alternative hypotheses play in determining the most accurate explanation for a phenomenon.

Using Slide 18, the instructor should explain: One of the gastroenterologists at the hospital who sent patient biopsies to the pathology department was a young clinician named Dr. Barry Marshall. He heard about Dr. Warren’s observations of bacteria in the patient biopsies and was intrigued. Drs. Warren and Marshall were convinced there was a more direct relationship between the bacteria and ulcers than other people believed. In order to establish this relationship, they needed a better test. Ask students to talk to their neighbors about the question posed on the slide: If you were working with Drs. Warren and Marshall to design a study to determine whether the bacteria caused ulcers, how would you do it? Depending on the time in the class period, the instructor’s desires and the background of the students in the class, this activity can take anywhere from 2–7 minutes.

As shown in Slide 19, Drs. Warren and Marshall designed a study in which they treated ulcer patients with antibiotics to see if the disease stopped. Later they determined the number of ulcers each person had.

Slide 20, Slide 21, and Slide 22 focus the students’ attention on the parts of an experiment. The instructor can take this opportunity to talk briefly about the important aspects of experimental design, such as the importance of including appropriate controls.

The questions posed in Slide 23, Slide 24, Slide 25, and Slide 26 require the students to predict the results of an experiment that would support each of the hypotheses. This can be done with their neighbors or individually; the amount of time given to the students will depend on their background and the amount of time in the class period. The questions illustrate that a well designed experiment will allow researchers to distinguish between two or more alternative hypotheses—in this case, the “old” excess acid hypothesis and the “new” bacteria-caused hypothesis.

Slide 27 reports the results from Warren and Marshall’s studies. Their results supported the new hypothesis that bacteria cause ulcers. Students will probably think: This is the end of the story, right?

The question on Slide 28 asks students what they would conclude given the results of Warren and Marshall’s study. While answer C is the best answer in light of the data, most doctors at the time did not agree. The instructor should explain to the class that while answer C is the best answer in light of the data, most doctors at the time certainly did not agree and would have argued that D or B was a correct approach. This question illustrates that accepted ideas in science are not easily overturned. More than one study, from more than one research lab with results supporting the “bacteria cause ulcers hypothesis” is necessary in order for this to become the accepted explanation across the scientific community. It gives the instructor the opportunity to discuss this with the class.

Slide 29 presents an application question that is used to summarize the scientific community’s understanding of the cause of stomach ulcers.

Epilogue (Slides 30–33)

In 2005, J. Robin Warren and Barry J. Marshall won the Nobel Prize in Medicine and Physiology. The Nobel Prize committee recognized that Warren and Marshall’s discovery changed humanity’s experience of peptic ulcer disease. H. pylori infects approximately 50% of the world’s population and is often passed from mothers to infants. Although some people will never suffer from the debilitating symptoms of gastritis and ulcers, many experience these at some point in their lifetime. People with long-term symptoms have a relatively high incidence of developing stomach cancer. The World Health Organization ranks stomach cancer as the second most deadly cancer worldwide. Warren and Marshall’s discovery changed peptic ulcers from one of the world’s most common chronic, debilitating diseases to one easily cured with a simple drug regimen.

In addition, their discovery opened new avenues of research into possible microbial causes of other chronic inflammatory diseases such as Crohn’s Disease, rheumatioid arthritis, and atherosclerosis. Moreover, because of the clear links between H. pylori, gastritis and stomach cancer, there is growing research interest in understanding the links between chronic infection, inflammation and cancer.

Assessment

This case was developed as part of an NSF-sponsored grant (# DUE 0618570) to determine whether clicker cases such as this one produced greater learning than the traditional lecture approach. As part of that project, the clicker cases had questions that were asked of students both before and after the class in which the material was presented. The questions were also used again during the final exam.

A transfer question was also developed for the case. This is a question designed to test whether a student could apply the knowledge that was given by the instructor in class to a new situation—a test of higher level thinking, according to Benjamin Bloom’s taxonomy of cognitive domain. This question, together with the additional pre- and post-case questions, are presented in the Answer Key.

Answer Key

Answers to the questions posed in the case study are provided in a separate answer key to the case. Those answers are password-protected. To access the answers for this case, go to the key. You will be prompted for a username and password. If you have not yet registered with us, you can see whether you are eligible for an account by reviewing our password policy and then apply online or write to answerkey@sciencecases.org.

References

Websites

The Helicobacter Foundation

http://www.helico.com/ Last accessed: September 16, 2008

This site contains basic information on the diagnosis, history, and prevalence of H. pylori.

Marshall, Barry, J. Helicobacter Pylori Research Laboratory

http://www.hpylori.com.au/index.html Last accessed: September 16, 2008

Links to a wide variety of information on H. pylori.

Nobel Prize in Physiology or Medicine 2005 Press Release

http://nobelprize.org/nobel_prizes/medicine/laureates/2005/press.html Last accessed: September 16, 2008

This press release has a short history of Marshall and Warren’s work with H. pylori and the widespread implications of their findings.

Journal and Newspaper Articles

Scheindlin, Stanley. 2005. A century of ulcer medicines. Molecular Interventions 5(4): 201–206.

Historical review of ulcer disease and treatments beginning with Dr. Beaumont’s observations of stomach functioning.

Sweet, Melissa. 1997. Smug as a bug. Sydney Morning Herald Aug 2, 1997.

Newspaper article containing a personal and professional biography of Barry Marshall. Accessed via: http://www.vianet.net.au/~bjmrshll/features2.html.

Videos

An End to Ulcers: A Journey of Discovery. 1998.

A 57-minute video available from Films for the Humanities and Science (http://www.films.com). Uses interviews with Drs. Marshall and Warren and others to describe the research that revealed H. pylori as the cause of peptic ulcer disease and the struggle to change the scientific understanding of peptic ulcers. DVD ISBN 978-1-4213-3805-7.

Slide Credits

Acknowledgements: This material is based upon work supported by the NSF Grant No. DUE-0618570. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of NSF. Many thanks to Eric Ribbens, Norris Armstrong, Hosun Kang, and all the other members of the “clicker team” for valuable feedback on earlier versions of this case.

Date Posted: October 10, 2008.

Copyright © 1999–2010 by the National Center for Case Study Teaching in Science.  Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.