Questions

1. Do you think it ethical and appropriate for Marshall to have used himself as a test subject and swallowed a sample of Helicobacter pylori? What precautions did he take? Would you do it? Why or why not? Answer: Many scientists have experimented on themselves. Marshall, for example, did not receive institutional approval for his self-testing. We think that making him as a test subject and swallowed a sample of Helicobacter pylori is unethical and inappropriate because the experiment might have a negative effect and not to mention the physical risks approaching the said microorganism. Doing the said experiment, he pre-medicated himself with the anti-acid drug cimetidine and also undergoes several antibiotic treatment. Taking a chance on a self-experiment is very risky and the route to success isn't always smooth so we would not do it for the sake of research. 2. How did the colloidal bismuth subcitrate (CBS) experiment provide evidence supporting Warren and Marshalls hypothesis? Answer: Before beginning a major study on the effects of H. pylori eradication on ulceration, Marshall did a pilot study in which he found that ulcer patients treated with bismuth had a substantially lower relapse rate than those treated with Tagamet. This study provided early support for the hypothesis that bismuth kills bacteria, thereby healing gastritis and preventing ulcer relapse. 3. Answer the following questions based on the data presented in Fig. 3: a. In Table II, of those patients with ulcers, how many were positive for H. pylori? Of those patients with normal endoscopic results, how many were positive for the bacteria? Answer: 26 out of 30 patients with ulcers had the bacteria. 8 out of 16 patients with normal endoscopic results had the bacteria. b. Based on this data, Warren and Marshall hypothesized that there was a causal relationship between ulcers and bacterial infection. But there were 4 patients with ulcers that were negative for the bacteria. Why is this not significant? Answer: Data that showed 4 patients with ulcers became negative for the bacteria is significant because those four had taken non-steroidal, anti-inflammatory drugs and the said drugs are known to induce ulcers. c. If there is a causal relationship between the presence of H. pylori and ulcers, how might you explain that 50% of the patients with a normal endoscopic examination were infected with the bacteria? d. In your own words, explain the results presented in Table III. What do you conclude from this data?

4. Robert Koch was a German physician who identified the bacteria causing anthrax and tuberculosis. His methods established four criteria that must be met for a specific pathogen to be considered the cause of a disease. These four criteria are listed below. For each one, discuss whether Warren and Marshall fulfilled them and, if so, how. I. The pathogen should be found in the bodies of animals having the disease. II. The suspected pathogen should be obtained from the diseased animal and grown outside the body. III. The inoculation of that pathogen, grown in pure cultures, should produce the disease in an experimental animal. IV. The same pathogen should be isolated from the experimental animal after the disease develops. Answer: Marshall and another volunteer tried to fulfill Kochs third and fourth postulates by ingesting cultures of the bacteria to confirm that H. pylori caused the gastritis and peptic ulceration. Both contracted gastritis underwent endoscopy and provided biopsies from which the suspected pathogen was re-isolated. This confirmed the connection between H. pylori and gastritis, but since neither scientist developed an ulcer, that link was still unproven. Marshall and a volunteer did not develop ulcers as a result of their experiment, thus all of the postulates has not been fulfilled. 5. What role did chance, assumptions, and curiosity play in Warren and Marshalls research on Helicobacter pylori? Answer: The chance, assumptions, and curiosity trigger Warren and Marshall to do research on Helicobacter pylori. Without these, no new discovery, no scientific breakthrough and no Nobel Prize. 6. Describe how the story of Warren and Marshalls discovery illustrates the process of science. Answer: The Helicobacter pylori story demonstrates so well how the understanding and sophisticated technology developed by basic scientists evolve into advances in understanding human disease and ameliorating it. It shows the significance of some factors like curiosity, questioning, opportunity, and persistence in scientific investigation. It shows how science is evolved upon the effort of others, and how assumptions can confuse peoples views. 7. How does this case illustrate the tentative nature of science? Answer: Their story shows the tenuous nature of truth in science that scientific truth can and does change when faced with new data and new interpretations. 8. How does this case illustrate the role of technology in scientific progress? Answer: The technological advances coming from basic research have allowed both rapid advancements in clinical research and rapid dissemination of the results. The task of culturing bacteria from individuals would be impossible. Not only were specialized equipment and techniques necessary to grow the bacteria, but also the only way to

obtain culture material from human sources was by endoscopy or internal examination of the stomach. 9. Why is this discovery significant? Do you think it is worthy of a Nobel Prize? Answer: When scientists identified Helicobacter pylori as an infectious agent responsible for peptic ulcer disease, it totally transformed our understanding of the microbiology and pathology of the human stomach. Thus, the work of Warren and Marshalls research on Helicobacter pylori is definitely worthy of a Nobel Prize. 10. What does the Helicobacter story tell us? What lessons can be learned from this story? Answer: The story of Warren and Marshalls discovery of Helicobacter pylori sounds like a history about the breakthrough of the microbes causing the infectious diseases that ravaged the worlds population. Dr. Marshall used himself as a guinea pig in order to satisfy Kochs postulates by using himself as a test subject and swallowed the H. pylori. An important lesson learned from Warren and Marshalls discovery is that not all infectious agents are easy to culture and isolate. In this regard, it is interesting that the colon, gall bladder, esophagus, and salivary glands are other sites in the gastrointestinal system where long-standing chronic inflammation predisposes to the development of some diseases. 11. Albert Gyorgyi, 1937 Nobel Laureate in Physiology and Medicine, once said in his Nobel award speech: Discovery consists of seeing what everybody has seen and thinking what nobody has thought. Describe how this statement applies to Warren and Marshalls pioneering work on peptic ulcer disease. Answer: