maps will lead researchers more quickly and much more cheaply to the genes they wish to find. They will enable younger researchers in smaller laboratories--those who now do not have the technological resources for genomic research--to apply their ample talents to research problems that now evade them. A second product of the Human Genome Project, the chemical sequence of human DNA, will give researchers the information they need to understand what genes actually look like. We must be able to "see" genes in their most exquisite detail before we can begin to learn how they function in health and malfunction in disease. The chemical sequence of human DNA will also offer the basis for strategies for development of new classes of drugs for treating diseases. With the establishment of Human Genome Research Centers at U.S. universities, NCHGR began its support of large-scale, high-resolution mapping of entire human chromosomes. These centers will focus on physical mapping of large, connecting expanses of human chromosomes as well as development of new technologies to store and analyze genome research data generated in these projects. NCHGR now supports large-scale mapping of chromosomes 4, 7, 11, and X. In the coming year, we plan to award new centers to expand our support of whole-chromosome mapping research. In addition, NCHGR-supported researchers began a large-scale effort to develop a physical map of the mouse genome. Because of the close similarities between the mouse and human genomes, this project will provide valuable information to the large number of health researchers who use the mouse in comparative studies to gain insights into the structure and function of human genes. Two important NCHGR initiatives begun in FY 1991 are aimed at delivering powerful new tools to the biomedical research community in a very short time. The first, an initiative to construct a "framework" map consisting of 300 or so evenly spaced, high-quality markers among the human chromosomes, is slated for completion in the next two to three years. As these markers begin to enter the public domain in FY 1992, this so-called "index" map will likely be the first research tool the Human Genome Project dispenses to the research community. Index markers are expected to be especially useful to scientists The in search of genes responsible for diseases and other biological traits. index map will serve as an extremely useful interim tool until the complete map of all the human chromosomes is finished, which we anticipate well before the turn of the century. With the second initiative, we have begun to tackle the technological problems of DNA sequencing. Sequencing DNA, or determining the order of its letters, is now the backbone of the body of biomedical research that seeks to understand how genes control cell function. Because DNA sequencing is very time consuming and expensive with current methods, the secrets of genes are locked away in indecipherable DNA sentences. These sentences consist of long strings of only four letters, ordered in very precise ways. If we could read these sentences easily, we would have access to the genetic instructions that control the chemical processes in our cells. We know already that errors in these sentences result in genetic defects and supply cells with misinformation about how to function normally. Several projects to improve the efficiency, accuracy, and cost of DNA sequencing were begun by NCHGR-supported scientists this year. These pilot sequencing projects will focus on biologically important sites in the human genome and on the genomes of model organisms, including the common intestinal bacterium E. coli, yeast, a roundworm, and another bacterium known as Mycoplasma, which are of broad interest to the large sector of researchers studying the basic biological structure and function of genetic molecules. Recent experience has shown that many of the genes of these model organisms are extraordinarily similar to human genes, so the knowledge gained will simultaneously benefit medical research. The main objective of these pilot DNA sequencing projects is to bring down cost. We will not support systematic sequencing of the human genome until costs are low enough and technology good enough to do it efficiently. This year we will begin supporting studies of molecules called complementary DNA, or cDNA. These molecules will lead scientists to DNA regions that are actually known to instruct a cell to produce proteins. some genome scientists are working to isolate large segments of human chromosomes, others will be using cDNA and other methods to develop new techniques to scan those regions for active genes. While In the past year, NCHGR also broke new ground in supporting the study of the ethical and social impact of new information about the human genome as it is translated into practical and clinical use. With approximately 4 to 5 percent of the NCHGR budget devoted to these studies in FY 1992, NCHGR has pioneered a new NIH participation in studies of the potential conflicts between the development of new medical technologies, personal freedoms, and social policy. Activities of the NCHGR Ethical, Legal, and Social Implica tions Program will be the point of entry through which the public voice on these issues will be heard. Public participation will be the best assurance that the benefits of genetic knowledge stemming from genome research will be maximized and the potential harms minimized. This past year the NCHGR ELSI program and its joint NIH-DOE working group have identified three major issues as priority research areas: privacy of genetic information in the context of insurance and employment as well as among members of extended families with inherited disease; safety and efficacy issues related to the clinical use of genetic tests; and the fair use of genetic information to avoid discrimination by insurance providers and employers. A task force assigned specifically to the issues related to insurance has begun a dialogue with representatives from the private health insurance industry and over the next year will convene public meetings and produce policy options on this complex matter. It is our hope that the knowledge and resources generated by this process will develop a body of thoughtful information useful to lawmakers should these issues require legislative action. Last year, soon after the gene for the common genetic disease cystic fibrosis was discovered--and a clinical test to detect the gene was developed-NCHGR co-sponsored a workshop on the appropriate use of the test to detect CF gene carriers. Workshop participants recognized that the testing issues evolving around the CF gene discovery are important not only with respect to CF itself but will also be relevant to a multitude of other diseases as their corresponding genes are discovered. Indeed, news stories about gene discoveries now appear regularly. NCHGR will be funding studies on how best to integrate evolving genetic tests into medical care. NCHGR is committed to increasing the number of students and faculty at minority institutions who will participate in the Human Genome Project. This past year, NCHGR staff has met with members of the Association of Minority Health Professional Schools and researchers supported by NIH's Research Centers in Minority Institutions program to discuss how minority institutions can become involved. Several groups have presented interesting ideas to us and we expect to receive applications in the near future. In addition, NCHGR has established a program to provide funds to faculty and students at minority institutions for travel to genome-related scientific meetings, courses, and workshops. Mr. Chairman, I believe NCHGR has made enormous strides in its first year to establish the administrative and scientific mechanisms needed to put the Human Genome Project on the sound footing capable of supporting this significant scientific research program. I have every confidence that this program will make important contributions to our knowledge about human biology, in particular toward the understanding of the thousands of human diseases that have their origins in faulty genes. The fiscal year 1992 budget request for the National Center for Human Genome Research is $110,487,000. Mr. Chairman, I will be pleased to answer your questions. Thank you. BIOGRAPHICAL SKETCH OF DR. JAMES D. WATSON Birthdate: April 6, 1928 Chicago, Illinois Education: 1947 B.S., Zoology, University of Chicago 1950 Ph.D., Zoology, Indiana University Professional Career: Research at the University of Copenhagen with Research at Cambridge University in the Cavendish Senior Research Fellow in Biology, California Institute of Research at Cambridge University in the Cavendish 1950-51 1951-52 1953-55 1955-56 1956-58 1958-61 1961-76 1968 Assistant Professor of Biology, Harvard University 1988-89 1989 Director of the Cold Spring Harbor Laboratory Director, National Center for Human Genome Research, NIH Awards: The John Collins Warren Prize of the Massachusetts General Eli Lilly Award in Biochemistry, 1960 Albert Lasker Prize (awarded by the American Public Health Research Corporation Prize (with F.H.C. Crick), 1962 4 nerican Academy of Arts and Sciences (1958) National Academy of Sciences (1962) Danish Academy of Arts and Sciences (1963) Honorary Fellow, Clare College, Cambridge University (1968) American Philosophical Society (1977) Atheneum (London) (1980) Royal Society (London) (1981) Academy of Sciences (USSR) (1989) MAPPING TIMEFRAME Senator HARKIN. There is another vote. I will have to see if I can hurry through this. We are talking about 15 years as sort of the plan to map and sequence? Dr. WATSON. Yes. Senator HARKIN. I asked you this last-well, was it last year or the year before. Dr. WATSON. Last year you asked me. Senator HARKIN. Can we collapse that timeframe some? Dr. WATSON. I don't think so. Senator HARKIN. Again, I want to know why not because you are talking about personnel and you are talking about computers. You are talking about machines. Dr. WATSON. We are going to get the maps. Depending on exactly how much money we get, we could collapse the mapping timeframe slightly, but we will get it done in 5 years. 38-711 0-91-37 |