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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

Mystery of the Seven Deaths Case Study Assignment Information: Purpose: To gain a further understanding of cellular respiration and how knowing the process can be utilized in a professional setting.

Skills: Soft Skills: These are skills that will be utilized in the professional world as you leave DCCC.   

This assignment will increase your critical thinking skills by helping you to make connections between the classroom and the career world. In this assignment you will practice the ability to problem solve as you determine cyanide lead to the deaths of these seven people. In this assignment (as in many fields) you will have to look at raw data and analyze it.

Content Skills: These are skills that will serve you well in this class and any subsequent Biology course.  

A better understanding of the reactants, products, and reactions of cellular respiration and how they are dependent upon each other. The ability to understand how cellular respiration can be influenced by targeting proteins.

Criteria: This assignment will be graded based upon correctness with the following point values per part.     

Part I = _________/ 5 pts (#1 – 3pts, #2- 2pts) Part II = _________/ 4 pts (#1 3pts, #2 – 2pts ) Part III = _________/ 15 pts (#1 – 12pts, #2 – 2pts, #3 – 1 pt) Part IV = _________/ 8 pts (#1 – 2pts, #2 – 2pts, #3 – 2 pts, #4 – 2pts) Total = _________/ 32 pts

“The Mystery of the Seven Deaths” by Michaela A. Gazdik

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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

The Mystery of the Seven Deaths: A Case Study in Cellular Respiration By: Michaela A. Gazdik Biology Department Ferrum College, Ferrum VA

Part I – The Symptoms Imagine that you work at the medical examiner’s office for a major metropolitan city. As Chief Medical Officer, you investigate suspicious deaths and provide toxicology services for the county. Unfortunately, it’s been a busy week. In the past five days, seven people have died, all with similar symptoms. It is your job to examine the data and determine the cause of death for these victims. The first was a 12-year-old girl. Her parents said that she was awake in the middle of the night complaining of a stuff y nose and sore throat. They gave her an extra strength Tylenol and sent her back to bed. At 7am the next morning, the parents discovered that the girl had collapsed on the bathroom floor. An ambulance rushed the girl to a nearby hospital, where she was pronounced dead. That same day, paramedics found the second victim unconscious on his kitchen floor after what they thought was an apparent heart attack. Sadly, the victim’s brother and fiancée also collapsed later that night while the family gathered to mourn his passing. Both had taken Tylenol to help them cope with their loss shortly before collapsing; neither survived. In the next four days, four other similar deaths were reported, all in the same neighborhood and all with similar symptoms. Are these seven deaths related? What is causing these people to die? It is your job to answer these questions before more deaths are reported. Symptoms exhibited by most patients: • • • • •

Dizziness Confusion Headache Shortness of breath/rapid breathing Vomiting

Most deaths were very rapid, occurring within a few hours of symptoms.

Questions 1. Are there any similarities or connections between these seven individuals? What questions would you want to ask the families to answer these questions? Yes, they all have multiple symptoms and took Tylenol. I would ask them: What symptoms occurred? How much Tylenol was taken?

“The Mystery of the Seven Deaths” by Michaela A. Gazdik

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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE 2. In your opinion, are these seven deaths connected? Why or why not? Yes, the seven deaths are connected because they all had symptoms and happened in the same neighborhood between five days.

Part II – Autopsy Report • Immediate cause of death was hypoxia (suffocation or lack of oxygen). • Tissue sections from heart, lung, kidney, and liver all show massive cell death. • Staining with specific dyes showed major mitochondrial damage within the affected tissues. • Oxygen levels in the patients’ blood were approximately 110 mm Hg (normal range is 75 – 100 mm Hg).

Questions 1. Recalling your knowledge of the function of organelles, what function of the cells was interrupted in these patients? Could this loss of function lead to the death of these individuals? Why or why not? The mitochondria was affected and took serious damage, no longer taking in oxygen and stopping the production of ATP. This could lead to the death of patients because the body needs ATP.

2. Given the data in the autopsy, were there any reports that seemed inconsistent with the immediate cause of death? Explain. They were diagnosed with hypoxia but had high oxygen levels. After the mitochondria is damaged, it’s not able to access oxygen to produce ATP in the body.

Part III – Subcellular Metabolite Analysis Detailed analysis of the damaged cells showed that ATP levels in the mitochondria were very low. Levels of pyruvate and acetyl coenzyme A (CoA) were normal. You begin to suspect a malfunction of a specific cellular metabolic pathway and so you request a more detailed analysis of the sub-cellular components of the affected cells from the autopsy. The levels of key metabolites are reported below: Average Metabolite Levels Metaboli te

Average Patient Levels

Normal Levels

Glucose

99 μM

100 μM

Pyruvate

27 μM

25 μM

NAD+

10 μM

75 μM

NADH

400 μM

50 μM

“The Mystery of the Seven Deaths” by Michaela A. Gazdik

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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

Questions 1. For each metabolite listed in the table, describe its role in cellular respiration? Are they substrates or products? What is their main function? Glucose is a substrate in glycolysis to make 2ATP + 2Pyruvate Pyruvate is normally a product but becomes a substrate after Kreb’s cycle—giving it 2ATP and lactic acid Oxygen, 34 ATP is produced from the ETP

2. Are there any abnormalities in the levels of these metabolites in the victims? Develop a hypothesis about which pathway may be affected based on these abnormalities. The abnormalities in the levels would be NAD+ and NADH. From the lack of ATP being producsed by the mitochondria, it willl not be able to turn NADH and FAD2 into NAD+ therefore leaving excess NADH.

3. Explain your reasoning for your hypothesis. Without NAD+ making ATP, the cells are going to have a shortage in energy.

Part IV – Role of Cyanide You are now convinced that you know the cause of death for these victims and quickly report it back to the police as this is a very dangerous situation. After realizing that the electron transport chain was no longer functioning, you started to suspect poisoning and ran a blood test for various poisons that you knew affected the electron transport chain. The test of all seven patients came back positive for cyanide. Cyanide irreversibly binds to cytochrome c oxidase (CcOX) of the electron transport chain and prevents the transfer of electrons to oxygen, the final electron acceptor.

Questions 1. What affect would cyanide have on the electron transport chain and the production of ATP? Explain your answer. Cyanide eliminates NADH and FAD2 from being used to make NAD+ “The Mystery of the Seven Deaths” by Michaela A. Gazdik

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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

2. Given what you now know about the action of cyanide on cellular respiration, explain why the patients died of lack of oxygen while their blood oxygen levels were normal? Blood oxygen could not be used for energy. The ETC wouldn’t function and cells would die to lack of ATP 3. Would artificial respiration or oxygenation have saved these people? Why or why not? It wouldn’t save people because it wouldn’t help the mitochondria. It would add more oxygen into the body which is not needed.

4. Looking back at the information you have about the people before they got sick, suggest a possible source of the cyanide poisoning? How should public health officials and police respond to this tragedy? Tylenol have have been poisoned with cyanide. Public health officials and police should respond with a full investigation on the Tylenol taken.

References Baines, A.T., McVey, M., Rybarczyk, B., et al. 2004. Mystery of the toxic flea dip: An interactive approach to teaching aerobic cellular respiration. Cell Biol Edu 3: 62–68. Beck, M., Monroe, S., Prout, L. et al. October 11, 1982. The Tylenol Scare. Newsweek. Bell, R. The Tylenol Terrorist. Tru Crime Library, http://www.trutv.com/library/crime/terrorists_spies/ terrorists/tylenol_murders/2.html. Last accessed: Sep 29 2010. Campbell, N.A., Reece, J.B., Taylor, M.R. et al. 2006. Biology Concepts and Connections, 5th edition. Pearson Education Inc. Jones, M., Bickar, D., Wilson, M. T., Brunori, M., Colosimo, A., and Sarti, P. 1984. A re-examination of the reactions of cyanide with cytochrome c oxidase. Biochem. J. 220: 57–66. Leavesley, H.B., Krishnan, L.L., Prabhakaran, K. et al. 2008. Interaction of cycanide and nitric oxide with cytochrome c oxidase: Implications for acute cyanide toxicity. Toxicological Sciences 101(1): 101–111. Tifft, Susan. October 11, 1982. Poison Madness in the Midwest. Time.

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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

Photo in title block © Frank Jr | Fotolia.com. Case copyright held by the National Center for Case Study Teaching in Science, University at Buffalo, State University of New York. Originally published October 13, 2010. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.

“The Mystery of the Seven Deaths” by Michaela A. Gazdik

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