Scientists conduct
2.
Ask students how the structural data on the affected and unaf-
investigations for a
fected muscle proteins, obtained by X-ray crystallography, sug-
wide variety of rea-
gest a way that the virus could cause the disease.
sons, such as to dis-
cover new aspects
Accept all responses. It is possible that the affected muscle protein
of the natural world,
can interact with the virus protein because its structure is different
to explain observed
from that of the unaffected muscle protein. Students might wonder
phenomenon, or to
how this interaction could occur. They might speculate that the
test conclusions of
virus protein interacts with parts of the affected muscle protein
prior investigations or
around the opening that exists. It also may be that the virus protein predictions of current interacts with some other region of the affected muscle protein.
theories.
Alternatively, students may hypothesize that the virus causes the
hole in the affected muscle protein. In other words, this action
of the virus produces a muscle protein of changed structure and,
therefore, changed function.
3.
How might a drug be used to treat the disease?
This is another opportunity for students to relate structure to func-
tion. They might reason that the affected muscle protein inter-
acts with the virus protein and not the unaffected muscle protein
because the two muscle proteins have different structures. This
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Student Lesson 3
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difference appears to be characterized primarily by an opening
in the affected muscle protein. Therefore, perhaps a drug can be
developed to change the affected muscle protein’s structure to one
more like the unaffected muscle protein. A simple possibility is to
develop a drug to close the opening. Students may suggest other
possibilities as well. Do not limit their thinking or try to guide the
discussion one way or another.
4.
Direct student groups to their computers. Tell them that the
director of the Global Science and Health Organization has
requested that they evaluate four new drugs that are believed to
have potential to treat the disease.
5.
Give each student a copy of Master 3.4, Drug Discovery Evalua-
tion Form. They should use this form to record their observations and interpretations.
6.
Ask students to click on the link “Drug Discovery Laboratory” on
the unit’s desktop.
A memo appears that gives students the instructions for this activ-
ity. Students compare the unaffected muscle protein with a complex
formed by combining a drug molecule with the affected muscle
protein. Four different drug molecules are available. When students
close the memo, a short animation comes on that leads to a screen
on which appear the unaffected protein, the affected protein, and
the four drug molecules. Students can make observations about
their structures. Clicking on a drug molecule attaches that drug
to the affected protein. Students should use the slider to rotate the
two proteins and compare their structures.
The instructions to students are purposely general. Students should
conclude that the drugs have been designed such that they either
do or don’t convert the structure of the affected muscle protein to
one more like the unaffected protein. Students will observe that
none of the drugs interacts with the affected muscle protein to form
a structure that is exactly the same as the unaffected muscle pro-
tein. This, too, is purposeful and is intended to stimulate student
thinking.
Depending on the class time you have available, you can assign
groups all four molecules to evaluate or a limited number of mol-
ecules (one or two) to evaluate.
Part 3, Wrapping It Up
1.
Reconvene the class. Ask groups to share their drug evaluations.
What were the drugs apparently designed to do? Do any drugs
show promise for treating the disease?
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This discussion allows students to share thoughts about what they
have done. They should focus on results and interpretations. Stu-
dents should understand that the path to solving a scientific prob-
lem is long and complex and that technology plays a key role in the
process. They also come to realize that there are not always neat
solutions to problems.
2.
Instruct students to prepare a report that summarizes their work.
They are to present their group’s work, from development of a
research plan to drug discovery. It is acceptable for students to add
Content Standard A:
their own touches to the group effort, based on class discussions
Formulate and revise
and further reflection. They should focus on
scientific explanations
• justifying their choice of technology to solve specific problems,
and models using
• demonstrating an understanding of specimen size and resolu-
logic and evidence.
tion, and
• indicating a logical flow for using technologies of increasing
resolution to solve problems.
For classrooms using the print version of this activity
Teacher note: The print version of this activity is a “thought”
activity. It does not make use of the graphics found in the Web
activity, since these graphics do not always reproduce well. This ver-
sion of the activity is more open-ended than the Web version. It allows
students more latitude in formulating a research plan, since they are not
restricted by available resources. Most important in this activity is the
students’ reasoning. Why do they propose to use a given technology?
What results do they expect? How will this lead them to the next step in
their plan? Students work in groups to increase interaction and collabo-
ration.
Part 1, What Is It?
1.
Divide the class into groups of three or four students each, and
give each group a copy of Master 3.1, Memo from the Director,
Global Science and Health Organization.
2.
Ask students to read the memo.
3.
Show students the transparency of Master 3.5, Available Technologies.
Tell students that to help them answer the questions raised by the
director of the Global Science and Health Organization, the fol-
lowing technologies are available: observation by naked eye, light
microscopy, transmission and cryo-electron microscopy, and X-ray
crystallography. Remind them (as stated in the memo) that tissue
samples from affected and unaffected individuals will be available.
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4.
Give each group a copy of Master 3.6, Science Reference Manual.
Explain to students that as scientists, they need reference materi-
als to help them develop a logical and realistic research plan.
Tip from the field test: Field-testing indicated that it is very useful
for teachers to introduce students to the Science Reference Manual
early in this activity (see Teacher note 1 on page 79). This resource
Content Standard A:
contains valuable information to help students formulate their
Design and conduct a
hypotheses, such as sizes of biological structures and resolution
scientific investigation.
limits of various technologies. It also contains information about
unfamiliar technologies, such as X-ray crystallography, as well as
about blood cells, muscle cells, and pathogens and how they cause
disease. At a minimum, you should introduce students to the Table
of Contents of the Science Reference Manual and point out the
information provided there.
5.
Ask students how they will begin their studies. What should
they do first? Encourage student participation and accept all
responses.
Teacher note: Even though students are in smaller groups of three
or four, work with the class as a whole through Step 14 to help
them understand the process they will follow.
This question to students is purposely vague. Its intent is to engage
the students and their imagination. Responses may vary consid-
erably. Some students may suggest beginning at the lowest level
of resolution, the eye, and visually confirming the presence of ill
individuals. They may suggest talking with healthy and ill individu-
als to gain clues about the nature of the disease. They may want
more details about symptoms. Indicate to students that while gain-
ing additional information by talking with affected and unaffected
individuals might be helpful, there is no time to travel. They need
to get down to business and begin investigating the issues raised in
the director’s memo.
6.
Direct students to the first question in the director’s memo.
Choosing from the available technologies, and using tissue sam-
ples from affected and unaffected individuals, how can they con-
firm the presence of disease at the cellular level in the affected
population?
If students ask what tissue samples are available, ask them to con-
sider which tissue samples they would want and why. Students
should reason that light microscopy can be used to look for the
presence of abnormal muscle cells in affected individuals. Unaf-
fected individuals should have normal muscle cells. Students
should provide a reason for wanting to look at any other tissue
samples.
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7.
Ask students, “Why would you use light microscopy to confirm
the presence of disease?”
Students should know that cells are too small to be seen by the
naked eye, although they can be seen easily with a light micro-
scope. If necessary, ask students to think about the information on
Master 1.1, Searching for Scale (the size of a cell) and what they
discovered in Lesson 2, Activity 1: Probing for Answers (start with
the largest probe, in this case visible light).
8.
After deciding on a starting point (light microscopy), students
should begin to create their detailed research plan. Master 3.2,
Research Plan, presents an example of how a research plan can be
organized.
Either give each student a copy of Master 3.2 or make a transpar-
ency of Master 3.2 to show the class. It is important for students to
see how information flows as an investigation proceeds and how
what is done at one step depends on results from previous steps.
The research plan is constructed as a modified decision tree: if I see
(result 1), I will do (next task); or, if I see (result 2), I will do (next
task).
9.
Use the transparency of Master 3.2, Research Plan, to demon-
strate how the research plan is constructed. Use Master 3.3,
Example Research Plan, as your guide.
10. Begin by writing the question, Is there evidence of disease at the
cellular level (in muscle cells)?, in the space next to the state-
ment, “To answer the question.” Ask students to help you deter-
mine which technology to use to answer this question.
Students should begin their studies with light microscopy to look
for the presence of abnormal cells in the muscle tissue of affected
individuals. Write this response in the space next to the statement,
“I will use this technology.”
11. Ask students to respond to the statement, “I chose this technol-
ogy because.”
Students should reason that cells are too small to be seen with the
naked eye but can be seen easily using a light microscope. In other
words, the resolution of a light microscope is sufficient to see indi-
vidual cells. Record the response on the transparency.
12. Ask students to state a hypothesis.
There is (or is not) evidence of disease in muscle cells.
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13. Ask students what two results they would expect.
Either abnormal muscle cells will be seen in affected individuals or
they will not. Record this response on the transparency.
14. Ask students what question they would answer next if they
observe abnormal muscle cells in affected individuals.
Students would proceed to Question 2 on Master 3.1, Memo from
the Director, Is the disease caused by an infectious agent? Record
this response on the transparency.
15. Ask students what question they would answer next if they do
not observe abnormal muscle cells in affected individuals.
There is no single response to this question. Students can use their
imagination.
16. Inform students that they are ready to begin their studies. They
should create their research plans in a manner similar to that
demonstrated.
17. Inform the class that results indicate the presence of abnormal
muscle cells in tissue samples from affected individuals but not
in unaffected individuals. First, they will address the question of
whether or not the disease is caused by an infectious agent.
Students now begin working in smaller groups.
18. The Science Reference Manual lists two common pathogens: bacteria and viruses. How could they identify one or the other as a
potential cause of the disease (that is, as being present in affected
individuals and not present in unaffected individuals) using the
technologies available to them?
They should name the technology they would use, justify their
choice based on the size of the objects they are looking for and the
resolving power of the technology, and indicate possible results
and what their next step would be. Allow groups no more than five
minutes to formulate their plan.
19. Ask a group to present its research plan very briefly.
Students should focus on the 10- to 100-fold difference in size
between bacteria and viruses. Light microscopy can be used to
resolve bacteria but not viruses. Students should understand that
they are following a plan analogous to that developed in Lesson 2.
They start with the largest probe available (visible light) to find out
about the largest possible structures that can be resolved.
86
20. Ask whether any groups have a different research plan.
Ask groups with a different research plan to make a brief presentation.
Use class discussion to resolve differences or reinforce similarities.
21. Inform the class that light microscopy did not demonstrate the
presence of any structures resembling bacteria in tissue samples
from affected or unaffected individuals. On the basis of this
result, students should now formulate the next step in their
research plan.
As before, students should name the technology they would use,
Content Standard A:
justify their choice on the basis of the size of the objects they are
Formulate and revise
looking for and the resolving power of the technology, and indicate
scientific explanations
possible results and what their next step would be. Allow groups
and models.
two to three minutes to confirm their plan.
22. Ask a group to present its research plan very briefly.
Students should use transmission electron microscopy to see
whether viruses are present in any of the tissue samples. Viruses are
readily visible with this technique, which uses a probe (electrons)
that is smaller than the probe they used initially (visible light). Ask
students to justify any other approach they suggest.
23. Ask whether any groups have a different research plan.
Ask groups with a different research plan to make a brief presentation.
Use class discussion to resolve differences or reinforce similarities.
Part 2, How Does It Work?
1.
Inform the class of the following results:
• transmission electron microscopy demonstrated the pres-
ence of viruses in blood and muscle tissue samples from both
affected and unaffected individuals,
• no other tissue samples contained viruses,
• there were more viruses in muscle of affected people than in
unaffected people, and
• the viruses appeared to be associated with actin filaments in
the muscle.
2.
Ask students to consider these results as they develop their plan
to answer Questions 4 and 5 on the director’s memo (Master 3.1).
For instance,
• How do students interpret the presence of virus and the
absence of disease?
• How might this relate to how the virus produces disease in
susceptible individuals?
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This may be a tough issue for students to deal with. It is not impor-
tant for them to come up with our scenario. It is important for
them to reason properly and use the available technologies to solve
whatever problem they perceive exists. They should consult their Sci-
ence Reference Manuals for helpful information.
A possible reasoned scenario is 1) virus is present in muscle tissue
of both affected and unaffected individuals because the virus binds
to a receptor in that tissue, 2) the virus nucleic acid codes for a
protein produced by the muscle cells, 3) the virus protein binds to
a key muscle protein in cells of affected individuals, which causes
the disease, 4) the virus protein does not bind to the muscle pro-
tein in cells of unaffected individuals, 5) the affected muscle protein
has a different structure from the unaffected protein, and 6) this
difference in structure allows the affected muscle protein to interact
with the virus protein.
3.
Ask groups to form a hypothesis based on their assessment of the
data presented in Step 1 of Part 2.
On the basis of the sample scenario presented in Part 2, Step 2,
one hypothesis might be as follows: the structure of the affected
muscle protein is different from that of the unaffected muscle pro-
tein. A related hypothesis might be that the virus protein binds to
the affected muscle protein and not the unaffected muscle protein
because of differences in structure between the two muscle pro-
teins. Another hypothesis is that the virus can attach to affected
muscle fibers and not to unaffected muscle fibers. There are many
possible hypotheses. It is important that each student hypothesis be
a testable statement that predicts a result.