Teacher Guide: Treatment, Enhancement, or Both? ACTIVITY OVERVIEW.

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1 Teacher Guide: Treatment, Enhancement, or Both? ACTIVITY OVERVIEW Abstract: Students consider potential gene therapy applications and categorize them as enhancements or treatments on a Venn diagram. The class then discusses each application and the difference between enhancement and therapy. Module: Gene Therapy: Molecular Bandage? Key Concepts: What qualifi es as a treatment? What qualifi es as an enhancement? Is there a case where a particular therapy could be considered as both? Some treatments could be applied as enhancements. Prior Knowledge Needed: A basic understanding of genetics; how mutations in genes may cause disease; a basic understanding of gene therapy. Materials: Student pages Appropriate For: Ages: USA grades: 7-14 Prep Time: 30 minutes Class Time: minutes Activity Overview Web Address: /teachers/tindex/ overview.cfm?id=gtvenn Other activities in the Gene Therapy: Molecular Bandage? module can be found at: /teachers/tindex/ Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT 84112

2 Teacher Guide: Treatment, Enhancement, or Both? TABLE OF CONTENTS Pedagogy A. Learning Objectives B. Background Information C. Teaching Strategies Additional Resources A. Activity Resources Materials A. Detailed Materials List B. Materials Preparation Guide Standards A. U.S. National Science Education Standards B. AAAS Benchmarks for Science Literacy C. Utah Secondary Science Core Curriculum Student Pages Directions and Venn Diagram Case Studies Questions Page S-1 S-2 - S-8 S-9 Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT 84112

3 Teacher Guide: Treatment, Enhancement, or Both? I. PEDAGOGY A. Learning Objectives Students will think critically about potential applications of gene therapy. Students will distinguish between the use of gene therapy to cure disease and the use of gene therapy for enhancement. Students will construct their own defi nitions of enhancement and treatment. Students will consider bioethical issues related to gene therapy. B. Background Information Note: It is important to remind students throughout this activity that the gene therapy applications discussed do not, as of yet, exist. This activity is meant to encourage critical thought about what additional applications might arise from successful gene therapy techniques and the bioethical issues those applications may entail. Many medical conditions result from mutations in one or more of a person s genes. Such mutations cause the protein encoded by that gene to malfunction. When this happens, cells that rely on the protein s function cannot behave normally, causing problems for whole tissues or organs. Medical conditions related to gene mutations are also called genetic disorders. If successful, gene therapy provides a way to fi x a problem at its source. Adding a corrected copy of the gene may help the affected cells, tissues or organs work properly. In this way, gene therapy differs from traditional drugbased approaches which may effectively treat the problem but do not repair the underlying genetic fl aw. However, gene therapy is far from being a simple solution that will automatically fi x a disorder. While scientists and physicians have made progress in gene therapy research, much work remains before its full potential is realized. Success in gene therapy depends on the effi cient delivery of the correct gene to the correct cells in the correct tissue. Scientists refer to DNA delivery vehicles as vectors. These vectors are designed to target specifi c cells. Traditionally, vectors have been derived from modifi ed viruses, including retroviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses. Other gene delivery approaches being examined include the use of liposomes, (lipidbased pockets that can carry plasmid DNA) or simply naked DNA with no carrier. Each vector and method of delivery varies depending on the specifi c disorder the therapy aims to treat. Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

4 Teacher Guide: Treatment, Enhancement, or Both? The only possible way to alter a gene in every cell in a human would be at the earliest stages of development, through germline or embryonic gene delivery. Germline gene delivery refers to the transfer of a gene into the cells that make sperm or egg cells. Embryonic gene delivery refers to the transfer of a gene into the cells of an early embryo, just after the sperm and egg unite. In both cases, the delivered gene would become a permanent part of all cells in the resulting adult. Scientists are looking to gene therapy as a way to treat genetic disorders. But what if the same gene delivery techniques, once established, could be used to change other traits, such as physical or behavioral traits? In the future, these techniques may open the door to genetic enhancement and the creation of socalled designer babies. In theory, scientists could someday alter any physical or behavioral trait that is controlled by genes. The reality of genetic enhancement is far less likely, however. To date, scientists know very little about the specifi c genes that contribute to any given trait. In fact, most human traits are controlled by multiple genes. Secondly, no human trait is determined solely by genes. Environmental factors play a large role in determining how traits develop in a person. So, even if the genes to alter were known, the outcome could not be reliably predicted. In sum, most traits are so complex that the concept of enhancement will likely remain in the science fi ction realm for all time. C. Teaching Strategies 1. Timeline 1 day before activity: - Copy student pages (S-1 to S-9) Day of activity: - Discuss the basic idea behind gene therapy - Hand out student pages - Have students consider whether each potential gene therapy application is a treatment, enhancement, or both - As a class, discuss the students decisions Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

5 Teacher Guide: Treatment, Enhancement, or Both? 2. Classroom Implementation Begin class by discussing that gene therapy is a way to treat genetic diseases by adding a normally functioning gene to take over for a defective one. Vectors designed to target specifi c cells are used to deliver the normal genes. Each vector and method of delivery varies depending on the specifi c disorder the therapy aims to treat. You may also want to discuss with students the challenges to gene therapy such as targeting enough cells to make a collective difference, incorporation of the new, desired gene, and the difference between treating adult cells, embryonic cells, or germ-line cells. Discuss with students the fact that gene therapy is still very much in the experimental phase with minimal success. Tell students that for the purpose of this activity, you are going to move into the future and assume that gene therapy techniques have been developed and are successful. What might be some gene therapy applications? Would gene therapies developed to treat disease have any other applications? Hand out a copy of student pages S-1 to S-9 to each student. Instruct students to read through each potential application and place it in the area of the Venn diagram they feel is most appropriate (therapy, enhancement, or both). Students should write the title of the case study on the diagram. When students are fi nished placing each application on the diagram, instruct them to complete the questions on page S- 9. Begin a class discussion: Summarize the fi rst case study aloud and ask the students who consider it a treatment to raise their hands. Next, ask students who consider it an enhancement, then both to raise their hands. Discuss where necessary. Repeat these steps with all of the gene therapy case studies. Discuss the following: What is the difference between a treatment and an enhancement? What applications did you place in both and why? Does the ability to do something mean we should? Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

6 Teacher Guide: Treatment, Enhancement, or Both? Note: See Additional Resources for links to helpful background information about genetic disorders. 3. Extensions Create class defi nitions of enhancement and treatment. Individually, or as a whole class, have students decide whether in vivo or ex vivo gene therapy techniques would be most appropriate for each case study. 4. Adaptations Students may work in small discussion groups to complete the activity. Rather than a whole-group discussion, create smaller discussion groups. Divide the class in half or into small groups; assign each group or half different case studies to work with. 5. Assessment Suggestions Use the questions at the end of the activity as an assessment. 6. Common Misconceptions A misconception may be that scientists currently have the ability to alter the genome to enhance traits or produce desired characteristics. This in fact is not the case. Students sometimes think that gene therapy replaces a faulty gene with a functional copy. It is important that they understand this is not the case. Gene therapy endeavors to add a functional copy of the gene of interest in the hope that its function will counteract the effect of the faulty gene. II. ADDITIONAL RESOURCES A. Activity Resources linked from the online Activity Overview: /teachers/tindex/overview.cfm?id=gtvenn Website: Gene Therapy: Molecular Bandage? - information about the idea behind gene therapy, techniques, current status of trials and other related issues. Website: MEDLINEplus Health Information - a searchable health encyclopedia and informational tutorials. A service of the U.S. National Library of Medicine and the National Institutes of Health. Website: Genetics Home Reference - a consumer-friendly resource for information about genetic conditions and the genes responsible. From the National Library of Medicine. Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

7 Teacher Guide: Treatment, Enhancement, or Both? Website: News releases and information about Alba, the GFP bunny, and transgenic art. III. MATERIALS A. Detailed Materials List Student pages S-1 through S-9 one copy per student. IV. STANDARDS A. U.S. National Science Education Standards Grades 5-8: Content Standard C: Life Science - Reproduction and Heredity; hereditary information is contained in genes, located in the chromosomes of each cell; an inherited trait of an individual can be determined by one or by many genes; a single gene can infl uence more than one trait. Grades 9-12: Content Standard C: Life Science - The Molecular Basis of Heredity; in all organisms, the instructions for specifying the characteristics of the organism are carried in DNA. B. AAAS Benchmarks for Science Literacy Grades 9-12: The Living Environment: Heredity - genes are segments of DNA molecules; inserting, deleting, or substituting DNA segments can alter genes; an altered gene may be passed on to every cell that develops from it; the resulting features may help, harm, or have little or no effect on the offspring s success in its environment. The Human Organism: Physical Health - faulty genes can cause body parts or systems to work poorly. The Designed World: Health Technology - knowledge of genetics is opening whole new fi elds of health care. C. Utah Secondary Science Core Curriculum Intended Learning Outcomes for Seventh and Eighth Grade Science Students will: 1. Use Science Process and Thinking Skills c. Develop and use categories to classify subjects studied. Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

8 Teacher Guide: Treatment, Enhancement, or Both? Intended Learning Outcomes for for Ninth to Twelfth Grade Science Students will: 5. Demonstrate Awareness of Social and Historical Aspects of Science a. Cite examples of how science affects human life. 6. Demonstrate Understanding of the Nature of Science i. Understand that science and technology may raise ethical issues for which science, by itself, does not provide solutions. Biology (9-12) Standard 4: Students will understand that genetic information coded in DNA is passed from parents to offspring by sexual and asexual reproduction. The basic structure of DNA is the same in all living things. Changes in DNA may alter genetic expression. Objective 3: Explain how the structure and replication of DNA are essential to heredity and protein synthesis. - Research, report, and debate genetic technologies that may improve the quality of life (e.g., genetic engineering, cloning, gene splicing). V. CREDITS Activity created by: Andee Bouwhuis, South Hills Middle School, Riverton, Utah Jane Bridge, Taylorsville High School, Salt Lake City, Utah Mary Bucklew, Orem Junior High School, Orem, Utah Donna Capasso, Adele C. Young Intermediate School, North Logan, Utah Jonathon Tuttle, Hunter High School, West Valley City, Utah Molly Malone, Genetic Science Learning Center Louisa Stark, Genetic Science Learning Center Steven Kiger, Genetic Science Learning Center (illustrations) Funding: Funding for this module was provided by a Science Education Partnership Award (No. 1 R25 RR16291) from the National Center for Research Resources, a component of the National Institutes of Health. Genetic Science Learning Center, 15 North 2030 East, Salt Lake City, UT of 6

9 INSTRUCTIONS 1. Read the following case studies. 2. Decide if the gene therapy described would be a treatment, enhancement or both. 3. Write the title of the case study in the place you choose on the diagram below. Enhancement Treatment Both Permission granted for classroom use. 1

10 6'7" Case Study: A couple who are fans of professional basketball are planning on having a baby. They would like for the child to be at least 6 feet 7 inches tall and extremely muscular by the time he is 16 years old. This, according to the couple, will guarantee him a spot in the NBA. Height is a polygenic trait (a trait influenced by several genes) that can be influenced by human growth hormone. Gene therapy could be used to add multiple genes that control height to the embryo. Case Study: A couple s newborn son has just been diagnosed with achondroplasia, the most common form of dwarfism. Achondroplasia is caused by a mutation in the FGFR3 gene, which controls bone growth. This mutation causes a decrease in the rate at which cartilage turns to bone during development and particularly affects long bones in the body. Characteristics of this disorder include an average sized torso with disproportionately short limbs and a slightly enlarged head with a prominent forehead. In more than 80% of cases, achondroplasia is the result of a new mutation, not inheritance. In cases where it is not caused by a new mutation, achondroplasia is an autosomal dominant disorder. Prenatal screening for achondroplasia is available. Gene therapy could be used to add a normally-functioning copy of the FGFR3 gene to the child s bone cells. Permission granted for classroom use. 2

11 Case Study: A 36-year-old mother of three has been diagnosed with malignant melanoma. Although malignant melanoma only accounts for approximately 4% of all skin cancers, it is the most deadly. Melanoma begins in the cells of the epidermis that are responsible for making pigment (melanocytes). It shuts down the process that regulates normal cell division, causing cells to divide and reproduce at a higher rate and form tumors. The DNA of genes involved in the cell division cycle is often damaged in melanoma cells, probably caused by ultraviolet radiation. Gene therapy could be used to insert an antigen-producing gene into the woman s melanoma cells, triggering an immune response that would destroy the cancer cells. Case Study: A couple in Kansas is very concerned about the high incidence of skin cancer and skin cancer-related deaths in their family. It has been known for some time now that ultraviolet radiation from sunlight is a major contributing factor to developing skin cancer. Working the fields of the family farm means spending a lot of time outdoors constantly exposed to this type of radiation. A family history of skin cancer is also considered a risk factor for developing such cancers. Through pre-natal genetic screening, the couple has discovered that the child they are expecting carries the forms of genes that have been linked to skin cancer. Specifically, the child is carrying mutated forms of genes thought to be responsible for maintaining the normal cell division cycle. They wish to pursue pre-natal gene therapy to reduce the risk of skin cancer in their child. Permission granted for classroom use. 3

12 Case Study: The gene that codes for a Green Fluorescent Protein (GFP) found in jellyfish has been isolated, copied and used by scientists to mark gene expression in a wide variety of studies. The protein glows when exposed to the proper light source. By tacking the GFP gene onto genes of interest, scientists can easily see where these genes are expressed in an organism. In April of 2000, artist Eduardo Kac commissioned a French lab to inject the GFP gene into rabbit eggs. This produced an animal named Alba the GFP Bunny. Alba appears normal but glows green from every cell when placed under blue light. Alba is an example of what is known as transgenic art. Case Study: A six-month old girl has been diagnosed with cystic fibrosis. This disease is characterized by a buildup of very thick mucus in the lungs, making it difficult to breathe and causing frequent infections. Additionally, a buildup of mucus in the digestive tract blocks necessary digestive enzymes, leading to malnutrition. Cystic fibrosis (CF) is caused by a defect in the gene that codes for the protein that is responsible for chloride ion transport across cell membranes. The life span of people with this autosomal recessive disorder is shorter than average - approximately 30 years. Gene therapy could be used to add a normal copy of the CF gene to the girl s affected tissues. Permission granted for classroom use. 4

13 Case Study: Firemen, emergency medical technicians, policemen, doctors, nurses, dentists, and other health care workers are constantly exposed to infectious diseases while transporting and caring for people who have been hurt or fallen ill. These diseases range from minor to life threatening and are an obvious concern for all involved. Gene therapy could be used to enhance these people s immune systems. Case Study: A two-month old boy is brought into the emergency room with a severe respiratory infection. The infant s blood work reveals few B and T lymphocytes, the white blood cells responsible for fighting infection. Further tests reveal that the infant has Severe Combined Immune Deficiency (SCID), a genetic disorder that affects B and T lymphocyte production in the body. SCID, commonly referred to as bubble boy disease, is usually an X-linked recessive disorder, but can also be autosomal recessive in some cases. Common infectious diseases such as a cold, flu and chicken pox are life threatening to patients with SCID. Because people with SCID lack the necessary immune response, many die within the first year of life as a result of complications from these illnesses. Current treatment for SCID includes bone marrow transplants and monthly injections of antibodies collected from human blood. Gene therapy could be used to add the gene responsible for producing T and B lymphocytes to the boy s white blood cells. Permission granted for classroom use. 5

14 Case Study: A seven-year old girl feels fatigued most of the time and even the mildest forms of exercise, such as walking up a flight of stairs, leave her breathless. She periodically complains about bone, joint and abdominal pain. After conducting tests, her doctors have determined that she has sickle cell disorder. In this disorder, red blood cells contain a mutated form of hemoglobin that causes them to collapse into a sickle shape under low oxygen conditions, such as exercise. The sickled cells can clog blood vessels and do not do a proper job of delivering oxygen to tissues. This is an autosomal recessive disorder. Gene therapy could be used to add a normal copy of the gene that codes for hemoglobin to the girl s bone marrow, where blood cells are made. Case Study: Your neighbor has been complaining that he is having difficulty seeing at night and that his peripheral (side) vision is beginning to blur. Thinking that he needs a different eyeglass or contact lens prescription, he visits his opthamologist. He is diagnosed with retinitis pigmentosa, a disorder that will cause him to lose his vision until he becomes blind. Retinitis pigmentosa causes cells in the retina to degenerate. It may be inherited through a variety of ways, including autosomal dominant, autosomal recessive, or X-linked. Gene therapy could be used to add genes to cells in the man s retina so that the cells will produce substances that have been shown to slow the loss of vision. Permission granted for classroom use. 6

15 Case Study: A girl in your class usually comes to school completely bandaged from the neck down. You have been instructed to be very careful about pushing or bumping into her and you notice that she moves very carefully and deliberately. You learn that this student suffers from a severe blistering disorder called epidermolysis bullosa. People with this disorder have very fragile skin and mucous membranes that blister after the slightest amount of pressure or friction. The blisters fill with fluid and then scar when they heal, reducing the ability to move. People with epidermolysis bullosa lack a particular type of collagen fibril that anchors skin in place. The disorder is inherited; some forms are autosomal dominant while others are autosomal recessive. Occasionally, the disorder may also arise as a new mutation. Gene therapy could be used to insert a normal copy of the collagen-producing gene into the girl s skin cells. Case Study: A toddler you baby sit after school is having trouble walking and seems to fall more than other children his age. After extensive medical tests, the toddler is diagnosed with Duchenne muscular dystrophy. Muscular dystrophy causes a slow degeneration of the voluntary muscles until the muscles have little to no function. This degeneration is caused by the lack of a protein called dystrophin that aids in proper muscle function. Duchenne muscular dystrophy, the most common form is an X-linked disorder and begins to affect children at a very early age. Gene therapy could be used to add a normal copy of the dystrophin-producing gene to the boy s muscle cells. Permission granted for classroom use. 7

16 Case Study: A world-champion body builder notices that he must work harder and harder to keep his physique as he ages. His muscles just are not retaining mass and bulk like they used to. He also feels a very slight weakening of muscle performance as he is lifting weights. Body building competitions are a way of life for him and he hopes to compete for at least another 5 years before retiring. He would like to use gene therapy to add an additional dystrophin-producing gene to his muscle cells, which would improve and maintain muscle mass and performance. Permission granted for classroom use. 8

17 Answer the questions below: 1. Look at the treatment portion of your diagram. For you, what are the characteristics of the conditions for which gene therapy qualified as a treatment? 2. Look at the enhancement portion of your diagram. For you, what are the characteristics of the conditions for which gene therapy qualified as an enhancement? 3. Agree or Disagree: Most conceivable gene therapy treatments could potentially have an application as an enhancement. Explain your answer using an example. 4. What other categories (such as preventative measure) could you add to your diagram? List them and describe the characteristics of the conditions that they would contain. Permission granted for classroom use. 9

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