Why is there no GENE THERAPY section in this BIOMEDICAL ETHICS area? -- Part 1 Reply by Jack P. Freer, MD This is an important area for discussion; thanks for raising the question. In order for readers to understand some of the ethical issues related to the important field of genetics, I will provide a rather lengthy explanation of some background material now, and develop these ideas further in future messages. There are two major categories of genetic therapy currently under investigation: somatic and germ-line. Understanding the difference is necessary to follow the ethical debate about such treatments. A large number of personal traits (including personal physical features, personality characteristics, and illness susceptibility) are now understood to be under genetic control. That is to say, much of who we are is determined by the genetic information built into our cells at birth. In regard to diseases, this includes the typically "genetic" disorders (such as hemophilia and sickle cell disease), but also less well defined tendencies to develop cancers or Alzheimer's disease. Although we don't understand all the details concerning how these illnesses are made more likely by our genes, we continue to learn more with each passing day. Theoretically, it is possible to (someday) reveal a large amount of information about how how many many people are predisposed to various illnesses. The basic mechanism of genetic information transfer is a two step process. We have two kinds of cells in our bodies: somatic cells and germ cells. The somatic cells are the vast majority of cells in our bodies and constitute the material which makes up most of our organs and tissues. Germ cells however, are quite different. They are the reproductive cells which are transferred from generation to generation and are located within our reproductive organs. They grow and multiply for the sole purpose of forming eggs and sperm cells to create new organisms. They also obviously contain the information about all the traits mentioned above (including susceptibility to illness), but don't affect THAT person. Rather, they affect his or her offspring (when the information is transferred to the child's somatic cells). Once we understand how these traits are transmitted and cause disease, we can try to interrupt the process. We can start by blocking or otherwise offsetting the disease process implemented by the somatic (body) cells. So for example, in cystic fibrosis, an hereditary defect prevents cells in the respiratory and intestinal tract from secreting important substances. This results in digestive problems and very serious lung problems. The failure to produce normal respiratory secretions leads to serious lung infections, and ultimately to an early death. Now, by treating the somatic (specifically, lung) cells missing genetic material, the cells can function normally, and infections can be prevented. That person however, can still transmit the gene for cystic fibrosis to his or her child, because the germ cells have *NOT* been altered. Somatic cell therapy treats the patient before us NOW, but if we could treat the germ cells, we could eliminate the disease in future generations. In future message, we will discuss the Human Genome Project, germ cell therapy, and ethical issues related to this topic. Part 2 Since 1990, much of the genetic research being done has been coordinated through the Human Genome Project. This is a multi- billion dollar, project based in several research institutions, whose goal is map the entire human genome. By identifying the various genes responsible for human traits, it is hoped that genetic illnesses can be better understood and prevented. Furthermore, as it appears many illnesses are in part due to genetic susceptibility, many "non-genetic" diseases might be better understood. Because of concerns about ethical and social implications of such research, the Human Genome Project established a program to study such ramifications. The following is a recent update of this group's activities from the Human Genome News and is available on gopher: In the next message, we will conclude with an overview of the various ethical implications of this research. ============================================= This section is from the document '/.INDEX/HGN/sept-94-hgn.data'. >From Dan's-Gopher Tue Jul 26 00:00:00 1994 Author : Drell Daniel Subject: DOE ELSI Program Enters Fifth Year Site : DOE OHER Source : Human Genome News, September 1994; 6(3):10 The DOE Ethical, Legal, and Social Issues (ELSI) Program, administered by the Office of Health and Environmental Research (OHER), aims to anticipate and study how individuals and society will be affected by the large amounts of genetic data being generated through the Human Genome Project. Three years ago, OHER narrowed its ELSI focus to concentrate on genetic education, privacy and confidentiality of personal genetic information, and genetics and the workplace [see HGN 4(2), 1p2 (July 1992) and 5(2), 3p4 (July 1993)]. Now entering its fifth year, the DOE ELSI Program added three new projects and two continuing ones to its portfolio of sponsored activities in FY 1994. To avoid unnecessary duplication of effort, OHER collaborates closely on program oversight with the ELSI Branch of the NIH National Center for Human Genome Research (NCHGR). In concert with the NCHGR ELSI Branch, the DOE program supported a recently released study by the Institute of Medicine on a range of ELSI issues, with recommendations for informed policies. Studies were also initiated on the implications of large DNA-based databanks and accumulations of data, including those under development by the Federal Bureau of Investigation, the U.S. Army, certain commercial companies, and academic research centers. Exhibits on genetics are being partially supported by DOE at both the San Francisco Exploratorium and the Smithsonian's Museum of American History. --New Projects-- At the University of Michigan Law School, Rebecca Eisenberg is studying the role of patents in transferring technology generated by the Human Genome Project to society at large Eisenberg will review available literature; query industry, government, and university sources about technology transfer; and explore several specific cases to see what works best for rapidly moving new technologies into the marketplace. The results of this study could affect DOE policy far beyond the genome program. Lee Hood, Valerie Logan, and Maynard Olson (University of Washington, Seattle) have begun an innovative program in which local high school students determine the sequence of STSs (sequence tagged sites) from cloned human genomic DNA. In addition to learning about human genetics, experiencing science firsthand, and contributing to the Human Genome Project by submitting their checked sequences to a DNA sequence database, the students will also explore ethical, legal, and social implications of the project. Insights gained through this experience may encourage some of them to consider the possibility of a scientific career. At California State University in Los Angeles, Margaret Jefferson and Mary Ann Sesma are translating into Spanish the Biological Sciences Curriculum Study module, "Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy." They will also introduce it to students in selected Los Angeles high schools. A key element of this approach is to involve parents so that cultural and family sensitivities and values can be incorporated into the study of genetics. In a project that may serve as a pilot for future curriculum development in other subject areas, knowledge about the genome project is being made available to a community not directly addressed by current educational outreach efforts. --Continuing Projects-- Troy Duster's "Pathways to Genetic Screening: Patient KnowledgepPatient Practices" is being renewed for a 2-year term. This project contrasts Caucasian understandings about cystic fibrosis with those of African-Americans about sickle cell disease. Early results suggest that communicating genetic information and understanding immediate health implications vary with factors that include social class, gender, and educational level. Duster also reports that detailed information is best obtained through personal contact and discussion in a familiar environment such as the home, rather than through an impersonal survey or doctor's office visit. The Cold Spring Harbor DNA Learning Center, under director Jan Witkowski, will continue for another year to hold workshops for opinion leaders and public policymakers on genomics and its implications for society. These workshops are aimed at educating individuals who could assist in introducing Human Genome Project information to society. Workshop attendees have included representatives from the media, genetic support groups, law and the courts, Congressional staff, state legislatures, government and private agencies, policy analysis programs, labor unions, and other organizations. --Potential Benefits vs Challenges-- The simple, persistent importance underlying ELSI studies is the recognition that each person has a unique genome that both identifies the individual and has predictive implications for future health. An "ideal" or "perfect" genome does not exist, even if such a concept could be defined. All genomes contain polymorphisms that could severely and adversely affect health under different circumstances or if not influenced or masked by other genes; this information about the individual has value to other people and groups who may have their own agendas. Potential benefits of human genome research for the enhanced health and well-being of humankind are very great, but the challenge is to manage this effort wisely and carefully and, if possible, avoid some of the foreseeable problems. [Daniel Drell, DOE OHER] Part 3 In this final message, I will attempt to provide an overview of the ethical issues surrounding (germ line) genetic research and intervention. The first type of problem concerns the preliminary work of investigating the human genome. The first step in treating genetic disorders is to identify exactly what genetic sequence is responsible for the trait. Currently available technology has permitted scientists to rapidly "crack the code" in the DNA molecules of our genes and chromosomes. While this is certainly a necessary first step toward *TREATING* genetic disorders, it is usually quite a while later that treatment/prevention is available (if ever). That means that there will always be a period of time in which we can identify individuals who will later develop illness, but have no treatment or prevention available for them. Knowing that one is genetically determined to develop an illness, and yet be unable to do anything with that knowledge is troublesome to many people. Furthermore, as suggested in an earlier discussion, this will also apply to many illnesses *NOT* usually thought of as genetic (such as Alzheimer's, alcoholism, and many if not all cancers). This is because the susceptibility to many diseases is also genetically determined. As our knowledge of the human genome grows, so will the list of diseases which can be predicted years in advance, with no hope of prevention. As troubling as that may be to some people, there are more serious consequences that will almost certainly occur. If a test becomes available which will predict an individual's tendencies toward certain illnesses, that will likely be exploited by insurance companies and employers. Just as life and disability insurers now require blood tests and physical exams to assure optimal health (or determine the cost of the insurance if "rated"), they will certainly wish to use the developing technology to determine if the applicant is at risk for diseases which will cost them money in the future. Similarly, employers would want such information to reduce absenteeism from alcoholism, etc. The second type of problem relates to the other side of the process, the actual genetic manipulation of germ line therapy. As we have suggested, somatic cell therapy is not terribly controversial because it does not alter the patient's germ cells. Any modification in somatic cells, ends with the death of that patient. Germ cell therapy however, alters the genetic make up of countless future generations. The sheer enormity of that impact is so awesome that it demands serious attention before we meddle with the very essence of what determines who we are. Thoughtful scientists have for some time, been concerned about the consequences of selective breeding livestock, and crops to meet our perceived needs. Invariably, there are surprises that could never have been predicted, since we never know ALL the different variety of traits and characteristics that derive from a given bit of genetic material. This unknowable information (ALL the future consequences of genetic manipulation) is a serious deterrent to germ line therapy in humans, since it will almost certainly be irrevocable once the change spreads through the population. Another aspect of this dilemma is the problem of "genetic enhancement." If we can alter genes to prevent illness, why not do it to enhance our offspring to make them "more desirable." They could be made stronger, smarter and more attractive if we choose. This is another frightening thought, since it raises serious issues about eugenics and how we treat people in our society who are "less desirable." I would like to stop at this point and invite readers to submit further questions or comments in regard to this issue. I have only given a brief overview and would be happy to pursue this further if anyone has specific thoughts on any of this. I will attempt to put together a reading list, but for now a good overview (although somewhat technical) is the issue of Journal of Medicine and Philosophy, vol. 16; no. 6 (1991). ---------------- Jack P. Freer, MD -- ********OFCN Biomedical Ethics Center ******** The OFCN Biomedical Ethics Center does not provide medical, legal or any other professional advice. Individual problems should be referred to a professional in the appropriate field. NOTICE: OFCN is not engaged in the rendering of professional medical services. 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