H O W- T O - D O - I T

Genetic S C R E E N I N G: A Unique Game of Survival

KAREN KURVINK

T

eaching the basics of genetic screening is fairly straight forward. DNA sequence information determined from the human genome projects will increasingly provide the basis for development of numerous diagnostic genetic screening procedures. These tests will in turn lead to more efficient monitoring and/or treatment protocols which could extend the individual’s survival. Eventually, diagnostic screening could lead to gene therapy and to cures for genetic diseases. In some cases, the treatment may actually occur before the clinical symptoms appear. What is more difficult to teach and/or for students to understand are the multitude of ramifications of these screening tests. Ethical and potential discriminatory issues abound. The following is a creative learning game that helps students reinforce

KAREN KURVINK is Associate Professor of Biology at Moravian College, Bethlehem, PA 18018; e-mail: kurvink@ moravian.edu. JESSICA BOWSER is a recent graduate (business major) of Moravian College.

JESSICA BOWSER

basic genetic information and facilitates the identification and understanding of these more subtle issues. The basic framework of the game was conceived by a business major taking my non-biology major course “Heredity and Society—Intertwining Legacy.” Obviously, the game is a unique modification of the popular TV program, “Survival.”

Introduction to the Game Initially students are given a brief introduction to genetic screening. It is assumed that they have read text information and/or attended a lecture on the topic. Each student is randomly given an index card indicating if he/she is in (a) the genetically screened population or (b) the non-genetically screened population. Students are told that each card also contains information that indicates their general state of health at various ages (the amount of information on the card can vary for different levels of students). The individuals in the screened population are required to briefly introduce the GENETIC SCREENING 435

class to the genetic condition diagnosed via screening. The non-screened individuals can share medical information at their discretion. The cards have information about the individual at periodic age stages: fetal, birth, 5 years, and at 10-year intervals until the individual dies. After sharing information, the group selects (via secret ballot) a member of the community to be eliminated. Students must reveal if their cards indicate death during the designated time period. These individuals are also eliminated. At the beginning of the exercise, each student receives a “torch” (a lollipop with an attached artificial flame), as occurs in the television series, Survival. When eliminated, the student’s torch is extinguished (paper flame removed). (Note, the student can be allowed keep the lollipop.) Eliminated students should move back from the game group and restrain from voting. They should, however, be allowed to participate in the discussions concerning the genetic diseases and the evaluation of the elimination results.

Elimination Voting The screening information may result in an individual being considered less genetically fit or it may help treat and/or cure the disease. After the secret vote, the reasons for the elimination are discussed. At this point some subtle social and political, as well as medical, reasons may emerge. When a death occurs, it should be discussed to determine if it could have been prevented, or at least delayed, with diagnostic genetic screening. In cases where death occurs later in life, the parents’ death may be the first indicator (red flag) a child has that he/she is at increased risk of having the same disease. The individuals who remain at the end of the game are not always the expected ones. If the class is large, students can be divided into smaller groups and, at the completion of the game, a comparison of survivors can be made.

Game Cards Game cards can be created by the students or the instructor. Examples of the card format are included at the end of the article. It is helpful to use two colors, one for the screened population and the other for the nonscreened population. If adequate class time is available, I prefer to have the students prepare the cards. It is an opportunity for them to select the diseases and to deduce the pertinent information about the disease on the cards. If they have access to the Web, they can search for information on the disease that will help design the cards. The OMIM (Online Mendelian Inheritance in Man) and GeneTests are excellent sites for this type of information. In some of the non-screened cases, general medical information related to a genetic condi-

436 THE AMERICAN BIOLOGY TEACHER, VOLUME 66, NO. 6, AUGUST 2004

tion may become available when the individual sees a physician with specific complaints or it may be discovered coincidentally during a routine physical exam. Remember this information does not have to be shared with the community during the various age conversations. If the students create the cards, the instructor should review their comments to correct errors and to offer suggestions before they are used in the class game.

Conclusion This is an interactive, fun exercise appropriate for either high school or introductory college classes that are involved in studying genetic screening. The goals are to reinforce genetic information related to screening and to generate situations where students can experience the various spinoffs of screening information which intertwine with social dynamics. Both the positive and negative aspects of screening generally become apparent. The key to a successful game is (a) carefully designed game cards and (b) an efficient, interactive moderator who keeps the game fun and progressive. The only cost involved is for lollipops and construction paper flames. The instructor may choose to conclude the game with a general discussion on the future of genetic screening. As genetic screening technology progresses, future babies may be tested for an increasing number of conditions before or at birth. Many questions arise concerning mandatory testing and application of the test information by the individual, the physician, insurance companies, and society in general. I frequently show selected sequences from the movie “Gattaca,” especially the sequence of a baby being screened for many diseases and the mother being criticized for producing a baby at high risk for cardiovascular problems. She had obviously not followed the accepted protocol for that period in futuristic time. Students appear to identify with the movie sequences and readily react with interesting comments and ideas.

References GeneTests. Online at: http://www.geneclinic.org/. Hamer, D.H., Hu, S., Magnuson V.L., Hu N. & Pattatucci, A.M.L. (1993). A link between DNA markers on the X chromosome and male sexual orientation. Science, 261, 320-326. LeVay S., & Hamer, D.H. (1994). Evidence for a biological influence in male homosexuality. Scientific American?, 270, 20-25. OMIM (Online Mendelian Inheritance in Man)—http:// www.ncbi.nlm.nih.gov/entreng/query.fcgi?db=omim

Card examples Non-Screened Population Diagnosis: Down syndrome

Diagnosis: phenylketonuria

fetus – no screening done

fetus – no screening done

birth – clinical symptoms associated with Down syndrome

birth – no screening done because family is temporarily living in India

5 years – placed in special education classes

5 years – reduced IQ, blond hair, and light skin and eye color

10 years – develops chronic myelogenous leukemia 20 years – dies from the disease Diagnosis: familial hypercholesterolemia

10 years – family returns to U.S. and individual is placed on a reduced phenylalanine diet but most of the mental retardation has already occurred

fetus – no screening done

20 years – institutionalized

birth – appears normal

30 years – has died, perhaps related to poor care in the institution

5 years – appears normal 10 years – appears normal 20 years – appears normal

Diagnosis: family history of breast cancer

30 years – clinical symptoms of high blood pressure diagnosed

fetus – no screening done

40 years – dies of heart attack

5 years – appears normal

birth – appears normal 10 years – appears normal

Diagnosis: mental retardation of unknown etiology

20 years – appears normal

fetus – no screening done

30 years – appears normal

birth – baby appears normal

40 years – lump noticed in right breast; surgery performed, followed by chemotherapy

5 years – normal growth but delayed intellectual development; placed in special learning classes 10 years – parents die in automobile accident; child becomes a ward of state – institutionalized 20 years – still institutionalized

50 years – ovarian cancer diagnosed; dies of metastasized cancer

Diagnosis: family history of schizophrenia

30 years – still institutionalized

fetus – no screening done

40 years – institutions closes due to lack of funds;

birth – appears normal

individual becomes a street person

5 years – appears normal

50 years – dies during a street assault

10 years – appears normal 20 years – clinical symptoms of schizophrenia

Diagnosis: retinoblastoma

30 years – has committed suicide

fetus – no screening done birth – problems diagnosed with eyes 5 years – has died of metastasized retinoblastoma

Diagnosis: cystic fibrosis fetus – no screening done birth – some clinical signs of cystic fibrosis (musty odor) 5 years – many respiratory problems 10 years – dies of CF

GENETIC SCREENING 437

Card examples Non-Screened Population continued Diagnosis: severe combined immunodeficiency disease (SCID) fetus – no screening done birth – diagnosed with SCID dies of infectious disease shortly after birth

Diagnosis: homosexuality fetus – no screening done birth – normal 5 years – normal 10 years – normal 20 years – sexually attracted to same sex individual 30 years – involved in homosexual relationships, loses job 40 years – diagnosed with HIV+ 50 years – treated for AIDS symptoms; dies of pneumonia

Diagnosis: dwarfism (achondroplastic dwarfism) fetus – no fetal screening done birth – small baby, diagnosed achondroplastic dwarf 5 years – some reduction in IQ; placed in special class, small child 10 years – same 20 years – frustrated in social life and job searching 30 years – happily married to another dwarf (positive assortative mating) 40 years – has a number of medical problems, treated 50 years – must use wheel chair; dies of unknown causes Diagnosis: family history of tall stature fetus – no screening done birth – large baby 5 years – measures in upper height distribution

Diagnosis: family history of diabetes mellitus type II

10 years – good basketball player

fetus – no screening done

20 years – plays basketball in college

birth – appears normal

30 years – plays professional basketball

5 years – appears normal

40 years – dies in auto accident

10 years – appears normal 20 years – some elevation of blood glucose 30 years – weight problems, more signs of diabetes, dietary regulation suggested 40 years – many diabetes-related problems

Get Involved with

50 years – dies of diabetes-related complications

Diagnosis: family history of obesity fetus – no screening done

Are you interested in becoming one of the following?

birth – big baby 5 years – obese kid 10 years – obese kid 20 years – obese young adult 30 years – obese, unsuccessful dieting, divorce, lost job 40 years – has surgery – somewhat successful but dies of heart attack

438 THE AMERICAN BIOLOGY TEACHER, VOLUME 66, NO. 6, AUGUST 2004

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Card examples Screened Population Diagnosis: Down syndrome

Diagnosis: Turner syndrome

Reason for screening: advanced maternal age

Reason for screening: short stature and failure to menstruate at age 13

fetus – chromosome screening associated with amniocentesis detects Down syndrome; parents decide to terminate the pregnancy

fetus – no screening done birth – apparently normal female baby 5 years – small, short stature

Diagnosis: homosexuality

10 years – same, some depth perception problems

Reason for screening: pregnant women has a brother who is gay

20 years – no menstrual cycle, under five feet tall – chromosome exam at age 13 indicated Turner syndrome (45 XO)

(Note: this screening is still speculative and based on the research of Dean Hamer at the National Institute of Health) fetus – amniocentesis – single gene screening indicates a high probability of homosexuality in male fetus birth – appears normal male

30 years – married, no children 40 years – same 50 years – same 60 years – same

5 years – normal 10 years – normal

Diagnosis: xeroderma pigmentosum (XP)

20 years – normal; self-declared homosexual

Reason for screening: an older sibling was diagnosed with XP

30 years – same

fetus – amniotic screening detects XP

40 years – same

birth – appears normal

50 years – same

5 years – care has been taken to avoid sun exposure

60 years – begins to demonstrate possible AIDS related symptoms

10 years – same

70 years – dies of AIDS opportunistic infections

Diagnosis: fragile X syndrome

20 years – same, frequent dermatologic exams, skin cancer discovered and treated 30 years – same, melanoma diagnosed dies of metastasized cancer

Reason for screening: familial history of fragile X syndrome fetus – chromosome screening associated with amniocentesis identifies a female baby with one X containing an expanded region in the area associated with fragile X

Diagnosis: phenylketonuria Reason for screening: mandatory in U.S. at birth fetus – no screening done

5 years – slight mental retardation noticed

birth – female; required PKU screening done, tests positive; placed on phenylalanine restricted diet

10 years – same

5 years – enters school, still on diet

20 years – marries and has a son with fragile X syndrome

10 years – off diet, appears okay

30 years – divorced, problems dealing with a severely retarded child

30 years – off diet, child is a bit slow mentally

40 years – on welfare

50 years – okay

50 years – on welfare

60 years – dies of heat exhaustion while playing tennis on an extremely hot day

birth – baby appears normal

60 years – dies of West Nile disease

20 years – married, pregnant, placed on diet again 40 years – okay

GENETIC SCREENING 439

Card examples Screened Population continued Diagnosis: hemophilia A

Diagnosis: Huntington’s disease (HD)

Reason for screening: pregnant woman’s father had hemophilia A

Reason for screening: Pregnant woman’s father had died of HD

fetus – no screening done

fetus – amniocentesis detects male with hemophilia A

birth – appears normal

birth – diagnosis confirmed

5 years – same

5 years – has been receiving recombinant VIII when bleeding episodes occur

10 years – same

10 years – same except a serious accident in Mexico requires a blood transfusion (blood was not tested for HIV)

20 years – decides to marry and requests HD screening; test is positive 30 years – starts to demonstrate HD symptoms

20 years – same (tests positive for HIV)

40 years – institutionalized

30 years – has died of AIDS associated opportunistic infections

50 years – dies

Diagnosis: Duchenne muscular dystrophy Reason for screening: none … hospital suggested the test for male fetuses and it was covered by patient’s insurance fetus – ultrasound determines the fetus is male; amniocentesis-specific DMD test is positive birth – baby boy appears normal 5 years – DMD progressing 10 years – confined to wheel chair 20 years – severe respiratory problems, dies

Diagnosis: severe combined immunodeficiency disease (SCID) Reason for screening: a previous male child dies of SCID shortly after birth fetus – amniocentesis – single gene screening test positive for SCID birth – special precautions against infections; gene therapy + ADA injections given 5 years – disease appears cured 10 years – still in good health

Diagnosis: Alzheimer’s disease Diagnosis: colon cancer Reason for screening: family history of early onset colon cancer

Reason for screening: family history of early onset Alzheimer‘s disease

fetus – no screening done

fetus – appears normal

birth – normal

birth – appears normal

5 years – normal

5 years – normal

10 years – normal

10 years – normal

20 years – individual requests a colonoscopy as part of a routine physical exam and polyps are discovered; screening for the associated colon cancer genes is performed and the individual is found positive; yearly colonoscopy exams recommended

20 years – normal – discusses possibility of inheriting Alzheimer’s disease with a geneticist. No definitive test is available; however, the association with Apo E4 and Alzheimer’s has been demonstrated and the individual decides to be tested for that. The test indicates ApoE4 homozygosity.

30 years – a new camera procedure is added to the routine colon examination to reduce the frequency of colonoscopy exams. Identified polyps were removed and biopsied. 40 years – although small intestinal sections have been removed, the individual is still alive and in good health

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30 years – appears somewhat forgetful 40 years – tests for Alzheimer’s – is ApoE4 homozygous 50 years – many Alzheimer’s clinical symptoms; dies of Alzheimer’s disease