Focus: Students discover some of the benefits of understanding human genetic variation at the molecular level by assuming the roles of employees of two fictional pharmaceutical companies to solve problems related to the development of new drugs.
Major Concepts: One of the benefits of understanding human genetic variation at a molecular level is its practical value for helping us understand and treat disease. The development of effective gene-based therapies is an exciting outcome of human genetic research. These therapies, however, are potentially many years away for many diseases.
Objectives: After completing this activity, students will
Prerequisite Knowledge: Students should understand the relationship among DNA, RNA, protein, and amino acids as well as how to interpret data displayed in tables.
Basic Science-Health Connection: This activity highlights the contribution that scientists studying human genetic variation at the molecular level are making to modern medicine. Research in genetics has made many contributions to clinical medicine across the last century. Research associated with the Human Genome Project is significantly changing not only how we think about human disease, but how we treat it.
Activity 3, Molecular Medicine Comes of Age, and Activity 4, Are You Susceptible?, focus students' attention on the practical, medical applications of understanding human genetic variation at a molecular level.
Activity 3 uses two vehicles—variable responses to drugs and the development of treatment strategies targeted at a disease's biochemical mechanism—to highlight some of the ways scientists can use molecular information to improve disease treatment. That is, Activity 3 focuses on those portions of Figure 6 that deal with pharmacogenomics and targeted drug therapy. An extension to Activity 3 invites students to consider gene therapy as another strategy made possible by a knowledge of molecular genetics.
Geneticists have long known that there is individual variation in the response to certain drugs. For example, in the early part of the 20th century, both Archibald Garrod and J.B.S. Haldane suggested that biochemical individuality as a function of genetic variation might explain people's unusual reactions to drugs and food. By the middle of the 20th century, biologists had identified several clear associations between certain genotypes and adverse drug reactions, including adverse reactions by some people to the drug succinylcholine, which is used as a muscle relaxant during surgery. If treated with this drug, individuals who produce a variant of the enzyme pseudocholinesterase, which normally metabolizes the drug, are in danger of extended depression of respiratory muscles and can suffer prolonged periods of apnea (cessation of breathing), which can be fatal. This is but one example of adverse drug reactions; a study reported in the April 15, 1998, issue of the Journal of the American Medical Association found that as many as 106,000 hospitalized patients per year had fatal adverse reactions to drugs. This would rank such reactions between the fourth and sixth leading causes of death in the United States.
Biologists also have long known that understanding the molecular structure of a disease-related gene can help them identify potential targets for intervention. As described in Understanding Human Genetic Variation, a striking example of this approach to combating disease is recent work on cystic fibrosis. Cystic fibrosis is the most common fatal genetic disease in the United States, affecting approximately 30,000 people. Currently, about half of those affected die by age 30. Since the identification in 1989 of the gene that is altered in cystic fibrosis, the pace of basic research has increased rapidly, and scientists are optimistic that they will be able to translate new knowledge about the molecular basis of the disease to new strategies to improve patients' lives.
In this activity, students assume the roles of employees of two fictional pharmaceutical companies, Firm A and Firm B. Each company is facing a significant challenge related to the development of a new drug. Firm A is developing a drug to treat asthma. Unfortunately, preliminary test results show variable and unpredictable effects. Students working as employees of Firm A must discover an explanation for these results and recommend a course of action. As students investigate this problem, they learn about the relationship between genetic variation and individual responses to drugs, and discover one way in which pharmaceutical companies are beginning to deal with this issue.
In contrast, Firm B wants to develop a new drug to treat cystic fibrosis. Students working as employees of Firm B discover first that most current treatments for this disease address its symptoms and not its cause. Students are then challenged to identify as many points as possible at which the biochemical processes underlying this disease could be corrected.
As students investigate this problem, they learn that knowing the sequence of a disease-related gene and understanding the disease's biochemical basis can help scientists develop exciting new approaches to treatment.
Because the benefits expected from both pharmacogenomics and targeted drug therapy are still largely unrealized, this activity is a bit futuristic and you may wish to acknowledge this to students. It is clear, however, that the era of molecular medicine—the application of knowledge about the molecular basis of variation to treating human disease—is already upon us. Although molecular medicine is just beginning to develop, the field has enormous potential for the improvement of personal and public health.
You will need to prepare the following materials before conducting this activity:
|Asking students to explain the phrase "understand human genetic variation at a molecular level" will help you assess what they learned from the first part of Activity 2.|
1. Introduce the activity by displaying a transparency made from Master 3.1, Molecular Medicine Comes of Age, and asking students what they think the statement means and whether they can think of any specific examples that illustrate or provide evidence for this point.
Students should be able to explain that understanding human genetic variation at a molecular level means identifying the specific differences in base sequence that distinguish one human from another. Although students likely will not mention pharmacogenomics and targeted drug therapy as examples of health care strategies that depend on understanding molecular variation, they may mention gene therapy as a strategy.
Students may have difficulty expressing these ideas in their own words. You may wish to help them by asking probing questions such as, "What does it mean to understand human genetic variation at a molecular level?" and "Can you think of any way in which finding and sequencing the gene related to a disease could help scientists develop ways to treat it?"
2. Explain that the students' challenge in this activity is to investigate two examples that illustrate and provide evidence for this point. Explain further that students will investigate these examples by acting as teams of employees in two pharmaceutical companies that are facing problems that threaten the companies' futures.
3. Divide the class in half and explain that one half of the class will act as employees in Firm A and the other half will act as employees in Firm B. Tell students that the problems the two firms face are different, but both problems can be solved in ways that relate to the statement on the transparency.
4. Direct students to organize into their teams. Distribute one copy each of Masters 3.2, 3.3, 3.4, and 3.5, Saving Firm A, [Role], to each team in one half of the class and one copy each of Masters 3.8, 3.9, 3.10, and 3.11, Saving Firm B, [Role], to each team in the other half. Also distribute one copy of Master 3.6, Report Form for Firm A, or Master 3.12, Report Form for Firm B, to each student and explain that the students should use these forms to organize their discussions and to report the results of their work.
As an alternative to using the masters provided for Firm A, you can have students use the equivalent videos on the Human Genetic Variation Web site.
5. Instruct the students to decide in their teams who will assume each of the four roles associated with their problem and to distribute the masters accordingly.
6. Give the teams 30 minutes to complete their reports and to be ready to defend their analysis of their company's problem and their suggested solution to the class, using the appropriate Report Form to organize their thoughts.
|An interesting way to assess students' understanding of this information is to ask one team to offer an answer to a question, and then ask a different team to evaluate the answer's accuracy and completeness and propose corrections or additions as necessary. This technique helps students learn to offer feedback in a positive way and extends accountability for acceptable answers to more students than simply the team members who provide the initial answer.|
When students reach Step 6 or Step 5 on the Report Form (Master 3.6 or Master 3.12, respectively), they will ask you, as vice president for the company, for additional data (Master 3.7, Some New Genetic Data, or Master 3.13, Some New Information). You can give the teams copies of the masters or you can simulate some mechanism that requires students to search for these data.
If students use the videos on the Human Genetic Variation Web site instead of the masters provided for Firm A, they will need to view the video Some New Genetic Data when they reach Step 6. Access to the video is password protected. You will need to give students the password: gene.
7. After the designated time, call the class to order. Explain that you will assume the role of the vice president for research for Firm A first and then the role of the vice president for research for Firm B, and that you are calling everyone together to hear the results of the teams' work.
8. Display a transparency made from Report Form for Firm A and use it to guide the discussion by asking teams from Firm A to present their answers to the questions (a different team should answer each question). After one team has offered an answer, invite questions and additional comments from the class.
To keep all students involved in both discussions, invite students from the other firm to contribute to the discussion by asking questions and even offering suggestions, as appropriate.
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