applications of understanding human genetic variation at a molecular level.
Lesson 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, Lesson 3 focuses on
those portions of Figure 6 (on page 25) that deal with pharmacogenomics
and targeted drug therapy. An extension to Lesson 3 invites students to
consider gene therapy as another strategy made possible by 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, people 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 have also 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 about 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. A recent article by scientists from the National
Human Genome Research Institute is an excellent review of the history and
current state of genomic medicine (Green et al., 2011).
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In this lesson, 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 of the ways 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 both pharmacogenomics and targeted drug therapy are still in their
early stages, this lesson 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.
Web-Based Activities
In Advance
Steps 4 and 6.
Materials and Preparation
Photocopies and Transparencies
Equipment and Materials
• 1 transparency of Master 3.1
• (Optional) Computers
• 1 copy of Masters 3.2–3.5 for each group
with Internet access
that will complete this part of the lesson
(Firm A)
• 1 transparency and 1 copy of Master 3.6
for each student who will complete this