• 1 copy of Master 3.13 for each Firm B group
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Student Lesson 3
Human Genetic Variation
Procedure
1. Introduce the lesson by displaying a transparency of Master 3.1,
Molecular Medicine Comes of Age, and asking students what they
think the statement means and whether they can think of any
examples that illustrate or provide evidence for this statement.
Students should be able to explain that understanding human genetic
variation at a molecular level means identifying the specific differences
in the base sequence that distinguish one human from another. Although
Asking students to explain
students will likely not mention pharmacogenomics and targeted drug
the phrase “understand
therapy as examples of healthcare strategies that depend on understanding
human genetic variation
molecular variation, they may mention gene therapy as a strategy.
at a molecular level” will
help you assess what they
Students may have difficulty expressing these ideas in their own words.
learned from the fi rst part
You may wish to help them by asking probing questions such as, “What
does it mean to understand human genetic variation at a molecular
of Lesson 2.
level?” and “Can you think of any way that 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 lesson is to investigate
two examples that illustrate and provide evidence for this statement.
Explain further that students will investigate these examples by
acting as groups of employees in two pharmaceutical companies
facing problems that threaten the companies’ futures.
3. Divide the class in half and explain that one-half will act as employees
in Firm A and the other half, 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 groups of four. Give one copy each of
Masters 3.2, 3.3, 3.4, and 3.5, Saving Firm A, [Role], to each group 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 group in the other half. Also give 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 students should use these
forms to organize their discussions and report the results of their work.
For an introduction to the different roles for Firm A,
students can view the Lesson 3 videos on the Human
Genetic Variation Web site. Go to http://science.education.
nih.gov/supplements/genetic/student and click on “Molecular
Medicine Comes of Age” to access the videos.
5. Instruct the groups to decide who will assume each of the four roles
associated with their problem and to distribute the masters accordingly.
Master 3.5, Saving Firm A, Role: Biostatistician, involves somewhat more
challenging analysis than the other roles. You may want to consider
assigning students who have stronger mathematical analysis skills to
the biostatistician role.
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6. Give the groups 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. They should use the Report Form
(Master 3.6 or 3.12) to organize their thoughts.
When students reach Step 6 on Master 3.6 or Step 5 on Master 3.12, they
will ask you, as vice president of the company, for additional data (Master
3.7, Some New Genetic Data about Firm A, or Master 3.13, Some New
Information about Firm B). You can give the groups copies of the masters, or you can devise an approach that requires students to search for the data.
Students can also go to the Human Genetic Variation Web
site and view the video “New Data” when they reach Step 6.
Go to http://science.education.nih.gov/supplements/genetic/
student and click on “Molecular Medicine Comes of Age”
to access New Data. Access to the video is password protected.
Give students the password: gene.
7. After 30 minutes, 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 groups’ work.
8. Display a transparency of Master 3.6, Report Form for Firm A, and use it to guide the discussion by asking groups from Firm A to present
their answers to the questions (a different group should answer each
question). After one group 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.
An interesting way
to assess students’
Question 1. What is the biological problem facing Firm A with respect
understanding of this
to Drug X?
information is to ask one
group to offer an answer
The response to Drug X among asthma patients is inconsistent, that is,
the drug does not work the same way on all patients.
to a question and a
different group to evaluate
Question 2. Describe asthma in your own words (refer to Master 3.2,
the answer’s accuracy and
Saving Firm A, Role: Team Coordinator , and Master 3.3, Saving Firm
completeness and propose
A, Role: Physiologist ).
corrections or additions as
necessary. This technique
Asthma is a fairly common condition that involves breathing
difficulties. The bronchioles contract abnormally. It is often associated
helps students learn to offer
with an allergic reaction to foreign substances.
feedback in a positive way
and extends accountability
Question 3. What is Drug X designed to do for asthma sufferers (refer to
for acceptable answers to
Master 3.2, Saving Firm A, Role: Team Coordinator , and Master 3.3,
more students than simply
Saving Firm A, Role: Physiologist )?
the group members who
The drug opens up the bronchioles to make breathing easier.
provide the initial answer.
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Student Lesson 3
Human Genetic Variation
Question 4. Look at the preliminary test results (refer to Master 3.5,
Saving Firm A, Role: Biostatistician ). Can you predict which group
will be helped most or least by Drug X? For example, does the sex of
an individual make a difference? Does having pets make a difference?
Explain your answers.
No to all three questions. Students should recognize that the proportion
of children who experience relief from the symptoms of asthma is the
same for males and females and for children who do and do not own
pets. In all cases, about one-third experience significant relief, slightly
more than 40 percent experience some relief, and nearly one-fourth
experience no relief. The constancy of these proportions means that
neither the sex of the individual nor the presence of pet dander makes
a difference in the response.
Question 5. What does the example of ApoE (refer to Master 3.4, Saving
Firm A, Role: Molecular Biologist ) suggest might be happening with
Drug X? Based on this example, what might Firm A investigate?
The data indicate that response to the Alzheimer drug might be based
on variations in the ApoE gene. Perhaps Firm A should explore genetic
differences with respect to response to Drug X.
Question 6. Firm A’s vice president for research (your teacher) will
provide you with some new data. What do the new data reveal
about Drug X?
There is a difference in response to the drug on the basis of the
genetic variations in the patient population.
Question 7. What would be an appropriate way to prescribe Drug X?
It would be appropriate to test each asthma patient’s genotype to
determine whether Drug X will be effective with that individual.
Question 8. Has your group solved the biological problem facing the
company with respect to Drug X? What new problems has it raised?
The group’s work has answered the basic biological question about
response to Drug X. It has raised new questions about the ability to
test all asthma sufferers. For example, how expensive is it to do that?
Will physicians order the test? Will it be covered by health insurance?
Who will have access to the information that results from the genetic
test? How will Firm A educate physicians and other healthcare
professionals so they understand the test and the results and can
explain this information to their patients?
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9. Repeat the same process with the groups from Firm B, but use a
transparency made from Master 3.12 to guide the discussion.
Again, to keep all students involved in the discussion, invite students
from the other firm to contribute to the discussion by asking
questions and even offering suggestions, as appropriate.
Question 1. What is the problem facing Firm B with respect to Drug Y
(refer to Master 3.8, Saving Firm B, Role: Team Coordinator )?
Drug Y is a successful treatment for cystic fibrosis (CF) and the firm’s
leading product. Firm B needs to keep looking ahead, however, and
begin thinking about new treatments for CF that take advantage
of what scientists have learned about the condition and, in the
future, might be able to supplement or even replace income that the
company is now receiving from Drug Y.
Question 2. Describe cystic fibrosis in your own words (refer to
Master 3.9, Saving Firm B, Role: Physiologist ).
CF is a genetic disease that causes the body to produce abnormally
thick, sticky mucus. This mucus clogs the airways and other ducts
and passages in the body and provides an ideal breeding ground
for many microorganisms. CF patients have frequent airway
infections and often show poor weight gain and slowed growth
and development.
Question 3. What have we learned in the past few years about
the cause of CF (refer to Master 3.10, Saving Firm B, Role:
Molecular Biologist )?
The most common CF mutation leads to one missing amino acid
in the CFTR protein. The loss of this single amino acid causes the
protein to be misshapen in such a way that most of it is destroyed
instead of being inserted into the cell membrane. The absence of
properly functioning CFTR protein in the cell membrane leads to
abnormal movement of chloride ions and water into and out of
the cell and the production of thick, sticky mucus.
Question 4. What is Drug Y (and most other current treatments)
designed to do for CF patients (refer to the Master 3.11, Saving Firm
B, Role: Physician , and discuss what goes in the last column of the
table provided)?
Most existing treatments for CF focus on alleviating the symptoms
of the disease—for example, removing airway mucus, reducing
infection, and improving nutrition. Students should discover this
by completing the last column in the table provided on Master 3.11.
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Student Lesson 3
Human Genetic Variation
Question 5. Firm B’s vice president for research (your teacher) will
provide you with some new information. What clue does this new
information provide about how Firm B might approach developing
new treatments for CF?
The important clue that students should gain from this new
information is that understanding the biological basis of CF has
allowed these researchers to propose a way to correct the problem in
CF cells. This approach is different from treating its consequences.
Question 6. What new approaches do you recommend Firm B consider
as it attempts to design and develop one or more new treatments for CF?
Students will not be able to suggest detailed approaches to developing
treatments, but they should be able to propose general approaches
that address each of the items on the flow chart on Master 3.10. For
example, students might suggest developing treatments that would
• correct or replace the defective CF genes,
• replace the missing amino acid in the CFTR protein,
• cause the CFTR protein to fold properly despite the missing
amino acid,
• prevent the defective CFTR protein from being destroyed before
it reaches the cell membrane,
• introduce functional CFTR protein into the cell from another
source, or
• create another mechanism in the cell that would regulate the
movement of chloride ions.
Question 7. Has your group solved the problem facing the company
with respect to Drug Y? What new problems has it raised?
No, the group has not solved the problem facing the company, but it has
You may wish to ask the
suggested several directions that the company may want to investigate
students who worked on
as it develops new CF treatments. New problems that the group’s work
Firm A’s problem to
has raised include problems common to all development of new drugs:
answer the questions
deciding on an approach to try, allocating funds to pay for development
and clinical testing, and going through the process of gaining Food and
related to Firm B’s
Drug Administration (FDA) approval for the new treatment.
problem, and vice versa.
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10. Challenge students to generalize what they have learned by answering
the following questions:
• How is genetic variation related to the use of drugs?
Students should understand that genetic differences between people
may cause them to respond differently to therapeutic drugs. As
scientists begin to detect such genetic differences, physicians will
become more sensitive to individual variation in response to drugs
and may even begin to prescribe drugs based on differences in
genotype.
• How will pharmaceutical companies likely use our increasing
understanding of human genetic variation?
Pharmaceutical companies may begin to design drugs intended
for people who have certain genotypes. They may also resurrect
Refocusing students’
products that were not viable in the past because of their
attention on the opening
unpredictable, negative side effects on certain people.
statement draws them
back to the lesson’s major
• How can discovering the genes associated with genetic disorders
concept.
help scientists develop new approaches to treatment?
As Figure 6 (page 25) shows, mapping and cloning the genes
associated with genetic disorders helps scientists discover their
underlying biochemical mechanisms, and this can suggest new
approaches to treatment.
Another way to raise these issues with students is to display a
transparency made from Figure 6 and ask students to explain
how the lesson they just completed relates to the beginning and
end points of the arrows on the diagram.
11. Display again the transparency you made from Master 3.1, Molecular
Medicine Comes of Age. Ask students to explain what it means, and
provide examples that illustrate or serve as evidence for this point.
12. Close the lesson by asking students what they think the
transparency’s title means.
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Student Lesson 3
Human Genetic Variation
Lesson 3 Organizer
Procedure
What the Teacher Does
Reference
Display a transparency of Master 3.1. Ask students what they think the
Page 90
statement means and whether they can think of examples that illustrate or
Step 1
provide evidence for this statement.
Explain that to investigate this statement, students will work in groups as
Page 90
employees of two pharmaceutical companies that are facing problems.
Step 2
Have one-half the class act as employees in Firm A and the other half, in
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Firm B. Tell students that the two companies face different problems, but
Step 3
both problems can be solved in ways that relate to the statement on the
transparency.
Direct students to work in groups of four. Give each group that will work
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as Firm A a copy of Masters 3.2, 3.3, 3.4, and 3.5. Give each group that will Step 4 *
work as Firm B one copy of Masters 3.8, 3.9, 3.10, and 3.11. Give each student a copy of either Master 3.6 (Firm A) or Master 3.12 (Firm B) and explain that these forms will help them organize their discussions and report their results.
Instruct groups to decide who will play each of the four roles and to
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distribute the masters accordingly.
Step 5
Allow 30 minutes for groups to complete their reports on Master 3.6 or
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3.12. When students ask for additional data, give them Master 3.7 or 3.13.
Step 6 *
At the end of that time, groups should be ready to defend their analysis
and to present their suggested solution to the class.
Call the class to order. Explain that you will assume the role of vice
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president for research first for Firm A and then for Firm B.
Step 7
Display a transparency of Master 3.6. Use it to guide the discussion about
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Firm A. After Firm A groups share their ideas, ask if other class members
Step 8
have questions or comments.
Display a transparency of Master 3.12. As before, use it to guide the
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discussion about Firm B.
Step 9
Challenge students to use these questions to generalize what they learned:
Page 95
• How is genetic variation related to the use of drugs?
Step 10
• How will pharmaceutical companies likely use our increasing
understanding of human genetic variation?
• How can discovering the genes associated with genetic disorders help
scientists develop new approaches to treatment?
Display again the transparency of Master 3.1. Ask students to explain the
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statement and provide examples.
Step 11
Close the lesson by asking students what they think the title on the
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transparency of Master 3.1 means.
Step 12
= Involves copying a master.
* = Involves optional online
video
vignette.
= Involves making a transparency.
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L E S S O N 4
Elaborate
Are You
Susceptible?
Focus
Students play a game to explore the relationship between genetic
At a Glance
variation and environmental factors in the onset of heart disease
and consider the implications for disease prevention of increased
knowledge about genetic variation.
Major Concepts
Studying the genetic and environmental factors involved in multifactorial
diseases will lead to better diagnosis, prevention, and treatment.
Objectives
After completing this lesson, students will
• understand that all disease, except perhaps trauma, has both a
genetic and environmental component;
• recognize that certain behaviors can increase or reduce a person’s
risk of experiencing certain medical outcomes; and
• understand that the ability to detect genes associated with common
diseases increases the prospects for prevention.
Prerequisite Knowledge