Super Scientists: How Mice Help Solve Disease PDF

 Helping Scientists Solve the Mystery of Disease C to you. ancer. AIDS. Alzheimer ’s, and heart disease. These are serious medical conditions that are surely familiar By creating “unhealthy”...

 Helping Scientists Solve the Mystery of Disease C to you. ancer. AIDS. Alzheimer ’s, and heart disease. These are serious medical conditions that are surely familiar By creating “unhealthy” or defective genes in laboratory mice, scientists learn how “good” genes function. So, as you can see, these im- portant animals help scientists discover new ways to predict, prevent, diagnose, and treat disease in humans. Maybe you have a friend or relative who actually has one of these diseases, or another condition just as serious. Did you know scientists are now working toward the time when such diseases may be prevented, or even cured? In reaching this goal, scientists must first better Pay Special attention to the high- understand the role that genetics and heredity lighted information. it will help you play in human disease. For instance, scientists are trying to answer questions such as why one member answer the questions on page 6. of a family may get cancer and another may not. To answer questions like these, researchers are using some unlikely “super scientists” in their work: laboratory mice. Despite their tiny size, these crea- tures pack a powerful punch in a relatively new field of study called transgenic research. This science allows researchers to transfer “healthy” and “unhealthy” genes from one organism (or living thing) to these laboratory mice so that better treatments can be developed to prevent and cure sickness. Through this research, scientists are breeding mice that develop human-like conditions—yes, mice that actually get human cancers, Alzheimer’s disease, or show signs of asthma and other sickness. How is this possible? Scientists change these labora- tory animals’ genetic material in the chromosomes, an important part of the cell that carries heredi- tary messages. We hope to understand which of our many genes (the material in our body that contains all our inherited traits) go wrong to make us sick. 1  Hi Kids, Let’s Talk About Genetics! HH ello, science students. My name is students. ello, science Dr. carol My macleod. name isIDr. am Carol Macleod, Ph.D. a scientist carol macleod. at the I am University a scientist of at the California, San Diego. I am a cancer University of California, San Diego. Igeneticist, am a cancerwhich means Iwhich geneticist, study genes means I in study cancer genes in and howand cancer they sometimes how may be may be they sometimes Think of DNA as a twisted ladder where hundreds inherited(passed inherited (passeddown downfrom fromone onefamily familymember of thousands of genes are strung together in pre- member to the next) and cause to the next) and cause disease. disease. cise order. These units of DNA contain the code to give your cells the proteins they need to help keep So that you may better understand my work and you healthy and to sustain life. However, if a gene the important role our laboratory mice play, let’s in the strand is missing, incomplete, damaged, or first talk a little about genetics—the branch of duplicated, it can cause disease. biology that deals with the heredity and differences This is very important when you realize that each in various living things. of your cells contains about 100,000 genes, and Just as genetics played a part in whether you were if just a single one is abnormal or changed, it can born with brown eyes or blue eyes and certain increase your risk of becoming ill. Combine this other characteristics that make us unique, genetics with other external factors (such as a poor diet also is a key factor in determining whether we and whether you smoke) and it can increase your may be susceptible to certain diseases. risk of illness even further. Your body contains about 60 trillion cells. Cells, This is where the laboratory mice come in. By as you may know, are the body’s building blocks. using specially bred mice in genetic studies, scien- Within the nucleus of each cell reside chromo- tists are learning the function of important genes. somes—essential genetic material that contains At the same time, other scientists are attempting to twisted, double strands of deoxyribonucleic acid discover and “map” the location and exact order of known as DNA, or the chemical containing the each of the 100,000 human genes on the chromo- “secret code” information for our bodies and all somes, much as you might use a map to find a city other living things. (Did you know that you have located on a river. As you may have heard in class 46 chromosomes—23 inherited from your mother and in the news, this effort is known as the Human and 23 from your father?) Genome Project. The use of these laboratory mice in the discovery and mapping of human genes will help us to better understand gene function and to discover which parts of a gene contribute or do not contribute to causing disease. In this way, better treatments can be devised to prevent or cure illness. Deoxyribonucleic acid 2  through Gene therapy/replacement, Mice have helped find treatments for genetic disorders and diseases like Breast cancer, Cystic fibrosis, Leukemia, and Multiple sclerosis. Why Use Mice? D id you know that 95 percent of all animals used in research are rodents? Mice are commonly used in transgenic research because their DNA structure is about 80 percent similar to that of humans. That’s pretty close, isn’t it? Like humans, mice are also mammals and their bodies have the same organs that work in very similar ways. Of course mice are tiny compared to humans, but their biology is very similar. Mice also make good research models because their life span is relatively long and their gesta- tion (the time from pregnancy to giving birth) is short. Did you know that an average mouse lives two years—and four weeks after birth, female mice begin to reproduce? This allows scientists to study generations of mice for long periods. Mice are also great research models because their size makes them easy to take care of and house. 3 Transgenic Researchers are Like Detectives Solving a Mystery! the offspring will contain the transgene and half L et ’s TALK et’s TALK aa minute minute about abouthow howscientists scien- will not. This ensures that with each generation conduct transgenic tists conduct research transgenic research. of mice born, there is always a “control” group with which to compare the transgenic mice. If the transgenic mice develop certain signs or Scientists can determine from family studies and symptoms associated with the disease being genetic testing if a particular gene seems to be studied, and if the control mice do not, then causing or contributing to a particular disease. scientists have proven a relationship between the suspected transgene and the disease. Like detectives trying to solve a mystery, scientists must first test their hypothesis, or hunch. This is Another approach scientists are using is called begun by locating, or isolating, the suspected “bad” gene “knockout” therapy. Instead of transferring human gene in the laboratory. After some special genes from one organism to another, “knockout” tests, they inject fragments of DNA containing the therapy involves the actual physical removal of a suspected bad human gene into the nucleus of a good gene from a living system and replacing that one-celled mouse embryo, or egg. gene with a defective one. Through this approach, scientists hope to do experiments that will help Let me illustrate how difficult this procedure is. us understand important details about the disease Once the DNA fragments are inside the mouse and, after that, to make more effective and speci- egg nucleus, there is only a 1 percent to 5 percent fic treatments. chance that the transferred gene will become inte- grated as part of the mouse chromosome in a useful way. We have found ways to determine exactly which cells have received the DNA frag- Our cousins, the Rats, have helped ments into their chromosomes. When the DNA is integrated, the transferred gene is then part with a lot of research too—developing of the animal’s genetic structure, or genome, penicillin and other antibiotics—the and is transmitted generation after generation. medicine you take when you get an ear After injection, the mouse embryos are implanted ache or are really sick! in the uterus of an adult female mouse. After birth, the baby mice are checked to see if they carry the integrated gene (now called a “transgene” because it has been transferred). When these transgenic mice become adults they will be bred with non- transgenic mice of the same breed, so that half of 4  The Future of Genetic Research ver the next few years, be prepared oO ver the next few years, be prepared to to hear and learn more about how hear and learn more about how genetic genetic science methods are opening science methods are opening new doors of new doors of understanding to what sci- to correct a gene understanding to what scientists believe could be entists believe could be as many as 4,000 inherited in an unborn child—a gene which may or as many as 4,000 inherited disorders. And because disorders. And because of their special qualities, may not develop into a disease sometime of their special qualities, laboratory mice will laboratory mice will continue to play a heroic in the future?” continue to play a heroic role! role! Such issues complicate, but do not detract from, the hope that genetic research offers. As advances in medicine continue, ethical questions about The purpose of this science is not to make whether science is going “too far” in its study of genetics you prettier or smarter, or make one group will be debated. This should challenge you to become better than another. The purpose is to more informed on the subject. Each of us will have to reduce suffering. This is our responsibility personally come to terms with questions like: “Is it right as scientists. Careers in Human Genetics Hey, readers: Check out these exciting careers in human genetics, and the training required. Clinical Geneticist and/or Researcher: Treats patients using Genetics Laboratory Technician: Helps the genetic laboratory information learned from genetic research. Requires a medical research assistant and others in genetic research studies. Requires degree from a medical school, and additional training in a spe- a bachelor’s of science degree in genetics, biological science, or a cific medical specialty such as pediatrics or internal medicine, related area. followed by special training in genetics. Vet Technician: Also known as a veterinary assistant. Assists the Medical Geneticist and/or Researcher: Performs genetic veterinarian with animal patient care, including lab tests, radiol- research in laboratories to help doctors treat patients. Requires ogy, surgery, and pet owner education and counseling. Requires a Ph.D. degree in cell genetics, molecular genetics, population a two-year associate degree in veterinary technology. genetics, or another related area, followed by additional study Veterinarian: Doctors of veterinary medicine are medical pro- in genetics. fessionals whose primary responsibility is to diagnose and treat Genetic Counselor: Counsels and advises patients and families diseases and other medical conditions affecting animals, and to who are involved in genetic research studies, especially those protect people from diseases transmitted by animals. In genetic who may be at risk, of a variety of inherited conditions. Requires research, veterinarians play an important role in supervising the a master’s of science degree from an official program in human proper breeding, raising, and care of animals used in science so genetics and genetic counseling. that scientists can better study diseases. Requires three to four years of college study in mathematics, chemistry, biology, and Genetics Laboratory Research Assistant: Assists the medi- other pre-veterinary medical coursework, followed by four years cal geneticists and others in conducting genetic research studies. of study at an approved veterinarian school. Additional study is Requires a master’s of science degree from an official program in also required after graduation. genetics/biological science. 5 QUIZ YOURSELF How well did you understand the information in this booklet? Test yourself and see how “gene smart” you really are! 1. _________ percent of all animals used in research are mice. 2. What is genetics? 3. What is transgenic research and what important questions are scientists hoping to answer through it? 4. In what ways are mice "heroes" in transgenic research? 5. Your body contains approximately _________ trillion cells and _________ chromosomes. 6. Explain how a mouse can actually get cancer, Alzheimer 's disease, or asthma. 7. Another term for deoxyribonucleic acid is _________. 8. There are approximately _________ genes in the human body. 9. A mouse's DNA structure is about _________ percent similar to that of humans. 10. why is transgenic research so difficult to Conduct? 11. How does gene "knockout" technology differ from transgenic science? 12. The primary purpose of genetic research is not to make you smarter or prettier but to _________ suffering and disease. 6  Handy Definitions Biomedical Research – Medical research based Geneticist – A scientist who studies genes and upon the principles of biology, biochemistry, their hereditary traits. and physical sciences in studying, diagnosing, Genome – A genetic structure and its DNA and treating disease. Such research often involves components. the use of laboratory animals. Gestation Period – The period of development in Cell – The basic structural and functional unit mammals involving the time span from pregnancy of life. to giving birth. Chromosome – A rod-shaped structure, located Heredity – The transmission of traits from parents in the cell nucleus that serves as the carrier of to their children or offspring. hereditary messages. Human Genome Project – A massive effort by DNA (deoxyribonucleic acid) – A string of scientists to discover and “map” the location and hundreds of thousands of genes situated in exact order of each of the 100,000 human genes in precise order within the cell that contains the an attempt to better understand gene function and “secret code” information for our bodies and to discover which parts of a gene contribute (or do all other living things. In addition, DNA gives not contribute) to causing disease. cells the protein we need to keep healthy and to sustain life. Life Science - The branch of science (such as biology and medicine) that deals with living Embryo – A mammal in the early stages of organisms and life processes. development before birth. Nucleus – The control center of all cell activity. Gene – A segment of DNA that controls a hereditary trait. Organism – Any living thing. Gene “Knockout” Therapy – An area of genetic Traits – Characteristics (such as skin color and eye science involving the actual physical removal of a color) passed on from parents to their offspring. healthy, or “good,” gene from a living system and Transgene – A gene that has been transferred to replacing that gene with a defective, or “bad,” gene another organism in transgenic research. in an attempt to help scientists better understand Transgenic Research – A relatively new area a particular disease or condition. of science which allows researchers to transfer Hypothesis - A tentative explanation for an obser- “healthy” and “unhealthy” genes from one vation, phenomenon, or scientific problem that can organism to another so that particular diseases be tested by further investigation. can be better understood, diagnosed, treated, Genetics – The branch of biology that deals with and eventually cured. the study of genes. Super Scientists is published jointly by the UCSD Office of Animal Research This project was made possible through the generosity of Merck Research Information, University Communications, University of California, San Diego Laboratories and the Charles River Foundation. (UCSD) and the California Society for Biomedical Research (CSBR). Additional copies may be obtained by contacting CSBR at (916) 558-1515. Writer: Michael Dabney, UCSD Editors: Marky Pitts, UCSD and Allison Chilcott, CSBR © 2004 by the California Society for Biomedical Research and the Regents of the Project Management and Design: UCSD Publications University of California. All rights reserved. 0304-026