of human genetic variation to a fictional case study involving a potentially
painful set of decisions that various members of a family have to make.
Groups of students analyze the case of a woman, Beth, who is concerned
that she may carry a variant of either the BRCA1 or BRCA2 gene that
predisposes people to breast cancer. The case study is presented in five
segments during which Beth makes two key decisions: (1) to proceed with
being tested for altered forms of these genes and (2) after she develops
cancer in one breast, not to have a prophylactic mastectomy of the other
breast. Students analyze each segment by discussing a set of questions
related to the underlying science and to the ethical and policy dilemmas
raised by the decisions.
The lesson’s fundamental purpose is to help students see that an under-
standing of science and a clear, systematic analysis of options can
help us make decisions in uncertain circumstances. Beth has a family
history of breast cancer, a form of cancer that kills more than 40,000
women in the United States each year. Information about the presence
of the altered gene could help her and her physician be more alert to
the possibilities of her developing cancer.
On the other hand, she is already practicing the guidelines recommended to
increase the chance of early detection should cancer develop. Furthermore,
as students learn, breast cancer related to the presence of an inherited
altered gene accounts for only 5 percent of the new cases of breast cancer
diagnosed each year, and even if Beth is shown not to carry the altered gene,
a certain risk of breast cancer remains. Thus, the decision whether to be
tested is complex and is made more so by uncertainty related to the normal
genetic variation that exists among humans. Our understanding of genetic
factors that can predispose individuals to certain cancers, while increasing,
is still far from complete. The question about whether Beth should request
prophylactic mastectomy of both breasts after she develops cancer in one
breast is equally complex.
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Web-Based Activities
In Advance
Steps 2 and 3.
Materials and Preparation
Photocopies and Transparencies
Equipment and Materials
• Make 1 copy of Master 5.1 for
• (Optional) Computers
each student*
with Internet access
• Make 1 copy of Master 5.2 for
each student
• Make 1 copy of Master 5.3 for
each student*
*Needed only by classes without access to the Internet.
Follow the instructions on page 110 to get to the Web site on the computers
students will use. If you do not have enough computers with Internet
access, you can use the print-based alternative (on pages 110 and 111).
Tips from the field test
Procedure
Teachers who tested this lesson raised two cautions:
• Students became so engaged in Beth’s story that they lost sight of the
major messages about genetic variation and its relationship to complex
disease. Remind your students that Beth’s difficult decisions arise
because of progress in basic science that allows us to detect such genetic
variations.
• Students tended to confuse the test for mutations in the BRCA1
and BRCA2 genes with a test for cancer itself. Be sure to clarify this
distinction. The genetic test identifies forms of the BRCA1 and BRCA2
genes that can increase one’s likelihood of developing cancer. It is not a
test for cancer.
1. Open the lesson by asking students whether they know anyone who
has had breast cancer. Invite those students who wish to briefly
describe their relationship to that person to do so.
With approximately one in eight American women developing breast
cancer in their lifetimes, it would not be unusual for one or more of
your students to be involved personally with this type of cancer. It
may be that the student’s mother or another family member has had or
currently has cancer. For some of those students, discussions of cancer
may be disturbing. We suggest that you watch your students for signs
of discomfort (for example, tearfulness, reluctance to begin the lesson,
and unusual silence or reticence) and provide appropriate support.
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Student Lesson 5
Human Genetic Variation
Steps 2 and 3 for classes with access to the Internet:
2. Direct students to organize into their small groups and watch the five
online videos under “Making Decisions in the Face of Uncertainty” (total
running time is about 10 minutes). This first time through, ask students
simply to watch and listen so they can get a sense of the complete case.
Go to http://science.education.nih.gov/supplement/genetic/student and click on “Making Decisions in the Face of Uncertainty” to access the videos.
3. Give each student one copy of Master 5.2, Analyzing the Issues, and
explain that now the class will view the videos again, one segment at
a time. Suggest that students take notes and list questions that occur
to them as they watch each segment, then respond to the related
questions on Master 5.2. Discuss each segment in turn, as students
complete it, using the questions on Master 5.2 as a guide. Address any
other questions the students raise as well.
Steps 2 and 3 for classes without access to the Internet:
2. Give each student one copy of Master 5.1, Making Decisions in the Face
of Uncertainty. Direct students to organize into their small groups
and to select students to read the parts of the various characters.
Ask students simply to read the script all the way through so they
can get a sense of the complete case.
3. Give each student one copy of Master 5.2, Analyzing the Issues, and
one copy of Master 5.3, Reference Database, and explain that now
the class will read the script again, one segment at a time. Suggest
that students take notes and list questions that occur to them as they
read each segment, then respond to the related questions on Master
5.2. Discuss each segment in turn, as students complete it, using the
questions on Master 5.2 as a guide. Address any other questions the
students raise as well.
If students raise questions about the science, legal, or policy issues that
you and they cannot answer with the materials provided, suggest that
someone pursue those answers outside of class.
Segment 1: Considering the Test
Question 1. What decision does Beth have to make?
Beth has to decide whether to have the test for mutations in her BRCA1
and BRCA2 genes. Your students might be interested in the financial
aspects of the test. As of 2010, when this module was reprinted, the
laboratory cost for the combined test for BRCA1 and BRCA2 ranged from
several hundred to several thousand dollars. There would be additional
110
costs for the associated genetic counseling. Insurance coverage varies
depending on the company.
Question 2. Who might be affected by Beth’s decision?
Beth, her husband, her mother, her sisters, her teenage daughter, and
her daughter’s future partner (if she has one).
Question 3. What arguments support having the test?
This is a good opportunity to ensure that the students understand the
underlying science in this case study.
For classes with access to the Internet:
The identifi cation of
Files in the online Breast Cancer Database will help students
mutations that predispose
learn about the science. Go to http://science.education.nih.gov/
individuals who carry
supplement/genetic/student and click on “Making Decisions in the
them to cancer is an
Face of Uncertainty” to access the database. Students can access those
excellent example of how
files on their own, if you have enough computers with access to the Internet.
basic research in science
yields results that benefi t
For classes without access to the Internet:
society. As students
Information in Master 5.3, Reference Database, will help
complete the lesson,
students learn about the science.
challenge them to think
Beth will no longer be uncertain about her status with respect to BRCA1
about the benefi ts that
and BRCA2. She will be able to make some other decisions, and she
Beth and her family
will be able to inform other family members about whether they are
gain as a result of this
at risk for carrying a mutated form of one of the genes. Note that Beth
knowledge. Ask students
says, with respect to a potentially negative genetic test, “You find out
that you’re safe.” Ask students to comment on this remark. Emphasize
to summarize their ideas
that this test identifies only one type of risk factor for breast cancer.
as you close the lesson
Simply because one does not have the particular mutations identified
in Step 4.
in this test does not mean that one “is safe” from developing breast
cancer. There likely are other unknown genetic variations that can
increase one’s risk. Furthermore, only a small proportion of breast
cancer is hereditary. Beth’s comment about birth control pills provides
an opportunity to discuss the constantly changing nature of scientific
knowledge and to point out the environmental contributions to cancer.
Question 4. What arguments support not having the test?
Beth may not want to know. She also will not have to worry about
whether she should share potentially positive test results with other
members of the family. She will not have to make tough decisions
about detection and/or prevention options (for example, prophylactic
mastectomy), none of which is 100 percent effective.
Question 5. What factors do you think Beth and Charlie should consider
in making their decisions?
Answers will vary, but be alert for misconceptions about the
underlying science.
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Student Lesson 5
Human Genetic Variation
Segment 2: A Family Question
Question 1. What new facts have you learned about breast cancer?
In testing for genes related to cancer, it is helpful to test a family
member who already has had the disease. Not all cancers are
heredity. The form of cancer that Beth’s mother has may not be
heredity. If it is hereditary, it may be associated with a gene not
yet identified by scientists.
Question 2. What are some of the family issues that arise in this
counseling session?
Beth’s mother feels guilty about her breast cancer and about the
possibility that she has passed on the associated mutation. The issue of
blame also arises, as well as the question of what Beth will do with the
information if the test is positive. Note that the counselor stresses the
importance of privacy and confidentiality. Emphasize for your students
that genetic counselors are trained to handle the social and emotional
aspects of counseling as well as the scientific aspects.
Question 3. What reasons does the genetic counselor give for not testing
Jennifer? Do you agree that children under 18 should not be tested?
The counselor’s reasons are rather nonspecific, simply that “teenagers
often have different perspectives about developing breast cancer.”
Students’ views on the testing of children under 18 will vary. Insist,
however, that they provide concrete explanations for their positions and
be alert to misunderstandings of the science.
The decision for a healthcare provider to conduct a genetic test is
based on a variety of factors. Healthcare professionals are trained to
reduce risks to their patients, including psychosocial risks. Anxiety
and depression may arise in response to a positive test. A similar issue
received attention in the mid-1980s, when healthcare professionals had
to decide how to handle testing for exposure to the AIDS virus, HIV. At
that point, the connection between a positive test for exposure to HIV
and development of the fatal disease AIDS was not yet clear (although
the correlation has since been established to the satisfaction of virtually
all scientists). Keep in mind that not everyone who inherits an altered
form of BRCA1 or BRCA2 develops breast cancer; thus, knowing that
one carries such an allele may trigger needless anxiety.
Other factors that a healthcare provider considers when discussing
genetic testing include the following questions:
• Can the related disorder, once diagnosed, be treated? In some cases,
for example, Huntington disease, there are no treatments currently
available that can help a person who tests positive.
• Does the patient exhibit symptoms, or is the order for a test based
on family history alone?
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• Do the benefits outweigh the harm brought about by knowledge of
the test results?
The issue becomes even more complex when the patient to be tested
is a minor, that is, under 18 years of age. The request for a genetic
test may come from the parents or from the minor. When the minor
is an adolescent, the issue becomes particularly complicated because
the patient may exhibit a considerable degree of autonomy regarding
his or her healthcare decisions. Experts agree that in these cases the
primary goal of genetic testing should be to promote the child’s well-
being. For example, the child who tests positive may be overindulged
or may be treated as a scapegoat. Both of these problems can occur,
however, even in the absence of testing. The testing of a child (or indeed
any other family member) also has implications for all members of the
family. In some cases, this forewarning will be welcomed; in others, it
may be unwanted. Genetic testing of a child will ease some aspects of
uncertainty, but people differ greatly in their response to such news.
In the case of genetic testing for mutations in the BRCA1 gene, most
healthcare providers and genetic-testing centers adhere to a policy that
denies tests to minors. This denial extends to requests from the parents,
who are the legal guardians of the child’s health. The psychological
effects can be mixed. Whereas some individuals prefer the release from
uncertainty, others could view a positive result as a death sentence
and react in ways that are destructive to themselves or their families.
Genetic testing requires informed consent, and some geneticists
argue that this requirement automatically rules out children, and
even teenagers, who generally are judged incapable of providing such
consent. This view of minors, however, may be far too broad and may
not be realistic. Some specialists are beginning to recognize that some
adolescents and young children have sufficient autonomy in consent
and decision making to make such decisions, and recommend that the
desires of these youths should be taken into account. In any event, one
must weigh the balance of potential harm and benefit in reaching a
decision about testing a minor.
One outcome of the current policy is to delay the decision to test until
the individual is an adult and can make the decision, rather than letting
parents remove this option by making the choice themselves. Note that
a change in policy most likely would result in parents being permitted
to make the decision, rather than leaving the decision to the minor in
question. Either way, issues of ethical decision making will arise.
Question 4. Beth’s mother says, “I’m not sure more information is better.”
Do you agree with her? Explain your answer.
Answers will vary.
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Student Lesson 5
Human Genetic Variation
Segment 3: The Test Results
Question 1. Beth and her mother have had the genetic test. What new
information have we learned?
Beth and her mother are positive for the BRCA1 mutation. Beth has a
lifetime risk of perhaps about 60 percent of developing breast cancer.
This number is down from original estimates, which were as high as
90 percent. Some recent data suggest a risk figure even lower than
60 percent. In fact, as is often true when a new medical test becomes
available, the exact figure is still unknown. Further, it appears that the
risk figure may vary, depending upon the particular mutation in the
BRCA1 gene that an individual woman carries.
Students have also learned that Beth may not develop breast cancer even
though her test was positive and that Beth can do a number of things
(breast self-examinations and mammograms, for example) to help
detect any cancer early and, therefore, to begin early treatment.
Remember to emphasize that Beth and her mother were tested for
mutations in the BRCA1 and BRCA2 genes, not for cancer.
Segment 4: A Diagnosis of Breast Cancer
Question 1. What new information have we learned about Beth?
It is now three years after the genetic test, and Beth has been
diagnosed with cancer in one breast. There is a high risk of cancer
in the other breast.
Question 2. What major decisions do Beth and her husband discuss in
this segment?
First, they discuss whether Beth should have both breasts removed,
and second, they consider whether to tell Jennifer that she is at risk for
the BRCA1 mutation. Note that even removal of both breasts does not
guarantee that the cancer will not appear elsewhere or even appear in
the remaining breast tissue.
Question 3. What do you think Beth and Charlie should do? Why?
Answers will vary, but make certain that students provide sound
explanations for their positions. Again, make sure that the science
is correct.
114
Segment 5: Jennifer’s Decision
Question 1. What new information emerges in this segment?
Beth has had a lumpectomy, and Jennifer has not been tested.
Emphasize that the chance of survival increases with early diagnosis.
Question 2. What is Jennifer’s primary concern about the test?
She is concerned that potential employers and insurers will discriminate
against her if they find out she has a high relative risk for breast cancer.
Question 3. Do you think employers or insurers should be able to deny
employment or insurance to a person who has a genetic predisposition to
a disease such as cancer? Explain your position.
Answers will vary. Inform students that at present many states have
laws that prohibit health insurers from accessing and using genetic
information in a discriminatory way. In addition, the federal Health
Insurance Portability and Accountability Act (HIPAA) prohibits those
who issue commercial, employer-based, group health plans from
discriminating against individuals on the basis of information gained
from genetic tests.
Regarding employment discrimination, the Equal Employment
Opportunity Commission extends Americans with Disabilities
protection to individuals who experience discrimination based on
genetic information related to illness, disease, or other disorders.
4. Close the lesson by challenging students to identify the questions
that now face Jennifer, Beth’s daughter, about her own health and
personal welfare. Encourage students to think deeply about these
questions. For each question that they identify as facing Jennifer,
have them determine her options and begin to identify arguments
Use students’ answers to
that she might use in support of choosing one option over the other.
these questions to assess
Invite neighboring groups to discuss these questions. Then, use the
their understanding of the
following questions to stimulate a brief, final class discussion about
lesson’s major concepts.
the lesson.
• Our understanding of and ability to identify genetic differences
among us has increased remarkably in the past few decades and
continues to increase. How might Beth’s and Jennifer’s decisions
have been different 50 years ago? What advantages does our
knowledge of human genetic variation bring us? What questions
does it also raise?
Fifty years ago, Beth and Jennifer would not have been faced with
the decision about whether to have these genetic tests. They most
likely would have undergone a radical mastectomy if cancer was
discovered. Our increased knowledge of human genetic variation
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Student Lesson 5
Human Genetic Variation
has improved our understanding of the relationship between certain
variations and disease and enabled us to test for some of these
genetic variations. New knowledge a