Policy Statement Archives

The Human Genome Project will impact significantly on all branches of human genetics, from the most basic research to the most practical clinical applications. The project also has social and legal implications that will impact mostly on human geneticists involved in patient care and genetic counseling. To assess this impact and to advise The American Society of Human Genetics (ASHG), the society formed the Human Genome Committee in the spring of 1990. At its first meeting in October 1990 the committee drafted a letter to Dr. James Watson, Director of the National Center for Human Genome Research. The letter, approved by the ASHG Board of Directors and sent from Dr. C. Thomas Caskey, then president of the society, and Dr. Ronald G. Worton, chairman of the Human Genome Committee, expresses support for the U.S. genome effort and raises some issues that are of concern to the human genetics community. The texts of this letter and of Dr. Watson's response are printed below.

As will be seen from Dr. Watson's letter, the genome project has shifted considerably over the last year or two and already recognizes some of these concerns. The genome effort now includes support for generation of markers that are useful in the study of genetic disease, analysis of expressed sequences that will be available as candidate genes for genetic disease, and direct support for the study of the legal and social aspects of genome research. This shift is a subtle one but an important one for human geneticists, and it ensures that the concerns of the human genetics community are being heard. In the months ahead the ASHG Human Genome Committee will solicit for the Journal short articles that will provide updates on various genome projects around the world.

The texts of the two letters follow:

• December 28, 1990
  Dr. James Watson, Director
  National Center for Human Genome Research
  National Institutes of Health
  Bethesda, MD 20892
  
  Dear Jim:
  
  The international effort to map and sequence the human genome has drawn considerable attention from the scientific and medical community. The sheer magnitude and cost of the project have raised some concerns about the priority of this research in relation to other, more traditional research. Furthermore, the potential for predictive genetic testing based on genome information has raised some concern in regard to the delivery of the anticipated diagnostic services and has raised fears concerning the ethical, legal, and social issues associated with confidentiality of the information and with its possible misuse by employers or providers of health insurance.
  
  The American Society of Human Genetics (ASHG), an organization of greater than 4,000 physicians, scientists, and genetic counselors, has within its membership the vast majority of American and Canadian health care personnel involved in the development and delivery of genetic services to the North American public. The Human Genome Project is therefore of particular interest to the ASHG, and conversely the ASHG believes that the views of its members will be highly relevant to the scientific community involved in the funding, promotion, and execution of the Human Genome Project. The ASHG has, through its Human Genome Committee, developed the following statement of support for the Human Genome Project and has attempted to define some of the issues that will most critically impact on its membership.
  
  Statement of Support
  
  The mapping and sequencing of the human genome will provide extensive new knowledge about the genes involved in inherited diseases, birth defects, later-onset diseases with a genetic component--including heart disease, neurological and behavioral disorders, and many forms of cancer--and even susceptibility to infection. This knowledge will have profound impact on the understanding, detection, prevention, and treatment of these disorders. To this end, the Human Genome Project is of tremendous importance in the field of medicine in general and in the area of medical genetics in particular. The ASHG therefore strongly supports the genome initiative and applauds the goals that we believe will result in better health care for the millions of people with genetically based disease.
  
  The nature of human genome research dictates that the large-scale accumulation of data must precede exploitation of the data for medical application. Of necessity, therefore, the project must focus much of its resources on the development of a high-resolution genetic map coupled with a detailed physical map of the entire set of human chromosomes, without being unduly distracted by the need to concentrate effort on specific disease genes. The ASHG supports this approach and recognizes that a single concerted international effort to map and sequence the genome is preferable to a series of smaller individual efforts-the concerted effort being necessary to reduce the extent of duplication of effort and to increase the chances of approaching closure of the map.
  
  While giving its support to the Human Genome Project, the ASHG has identified two major issues that deserve special attention from the planners of the human genome initiative. One is technology development necessary for the rapid and efficient use of genome information in the field of medical genetics; the second is the development of the infrastructure to enhance the dissemination of the new knowledge to the public, including the provision of educational programs for the medical community and the public.
  
  Technology Development
  
  The ASHG recognizes the single, most compelling argument in favor of the human genome effort to be the identification of the complete set of genes encoded on the human chromosomes-and the subsequent determination of the function of the encoded proteins or RNA. The identification of all the genes in a stretch of DNA is a nontrivial problem that requires the development of new technology that will allow the recognition of functional units. This would include, for example, both technology for the rapid and efficient isolation and mapping of cDNA clones from a variety of tissues and technology for the efficient recognition of regions of genomic DNA typically associated with expressed genes.
  
  Notwithstanding the general statement of support given above, the channeling of some resources into innovative schemes to pin-point, at an early stage of the project, those genes responsible for the most prevalent and most serious medical problems will have important ramifications for human health and can be easily justified as part of the overall human genome effort.
  
  In developing a genetic map that is of maximal use to the human genetic community, there will be great benefit in defining a standard set of 300-400 highly polymorphic markers (e.g., CA repeats) that can be used in segregation analysis for the localization of any disease gene. Resources allocated specifically for this activity will significantly enhance the research efforts of many scientists outside the genome project.
  
  Whether the genome project reaches the state where it is economically practical to sequence the entire human genome, there is still a great need for the further development of sequencing technology. Sequencing has become a mainstream technology of the human molecular genetics laboratory, both in a research capacity and in a diagnostic capacity. A significant reduction in the cost and a significant increase in the automation of sequencing will have a large impact on the human genetics community outside the Human Genome Project.
  
  Although the ASHG is concerned with the human genome more than with other genome, it recognizes that a complete understanding of the function of human genes may require the analysis of the genomes of other organisms. Simple organisms with small genomes (e.g., bacteria and yeast) may be subjected to detailed mapping and sequencing both in the process of technology development and as part of an effort to understand simple genome structure and function and genome evolution. Specific genes or selected chromosomal regions of complex organisms (e.g., mouse) may be subjected to partial analysis to provide a model organism that is better suited to genetic manipulation necessary for a detailed understanding of gene function.
  
  Infrastructure and Education
  
  The ASHG recognizes and is very much concerned that among the products of the genome effort will be the availability of new genetic probes for disease genes and for antibodies directed against the products of these genes, such reagents providing the ability to offer presymptomatic and prenatal testing for a wide range of congenital defects and adult-onset diseases. Two important ramifications that need to be addressed early in the genome project are (a) methodological problems related to the delivery of health care and (b) ethical, legal, and social problems related to the availability of sensitive information concerning the future health of an individual. Medical and public education will be a big part of the solutions to these problems.
  
  Delivery of health care.-The acquisition of new information does not guarantee the proper and timely use of the information, even when the course of action is readily apparent. Even now, the probes and other diagnostic reagents that are coming available as a consequence of disease gene cloning are having an important impact in genetic medicine. The recent discovery of the genes responsible for Duchenne muscular dystrophy and cystic fibrosis typify the problem, as a flood of diagnostic reagents are made available to a community largely unprepared for the task of providing for a whole new spectrum of diagnostic applications. The genome project must recognize at an early stage the potential for incorrect or inappropriate use of the new materials, by providing funds for training workshops, clinical training programs, laboratory director training positions, genetic counseling workshops, etc. Equally important is the development of national and international standards of practice and of standards for the quality control of diagnostic services, an area in which the human genetics community, including perhaps the ASHG, will wish to play an important role. To do so, however, will require the support of the planners of the Human Genome Project.
  
  Ethical, legal, social issues. - The acquisition of new information does not guarantee its use in a way that is to the benefit of mankind, respecting the prevailing views of society and the dignity of the individual. Members of the ASHG deal with such issues on a daily basis in their role as physicians, genetic counselors, and laboratory directors, providing sensitive and highly personal information about the future health of the individual and the family. There is a need for resources to fund a continuing dialogue on the ethical, social, and legal implications of the genome project. In addition to the workshops and symposia on this topic, there is a need both for careful research to establish the exact nature of the problems to be anticipated and for educational programs to prepare experts in legal and ethical decision making in the field of medical genetics. These needs arise not only out of the genome project itself; they are with us already as a result of the cloning of several of the most important disease genes. The genome project will, however, exacerbate the problem as the availability of diagnostic reagents for the common multifactorial diseases brings the technology to a much larger segment of the population and as screening programs for common genetic disorders brings the genetic knowledge to a majority of the population. Again, the ASHG may be able to play a significant role in the resolution of these issues, in partnership with the planners of the Human Genome Project.
  
  In summary, the ASHG gives its strong endorsement to the international human genome effort, recognizing the long-term benefit of the project to human health. We stress the need to devote some of the resources to technology enhancement, particularly in the area of disease gene identification and automated diagnostic testing. Furthermore, we suggest that the genome project has a major responsibility for the development of educational programs for the medical community and the public, this to be coupled with research into the social, ethical, and legal issues arising from the genome project. In this context, we applaud the fact that a significant sum has been set aside by the NIH genome center for the study of these issues. The ASHG is willing and anxious to assist the NIH, the DOE, and the genome programs in other countries in these important matters. In this regard, a new Human Genome Committee of the ASHG has been formed, and it has established three working groups to address (1) health care issues, (2) educational issues, and (3) legal, ethical, and social issues. This committee is formulating its own action programs and will be standing ready to assist the genome project in one of the most ambitious undertakings in the history of biological research.
  
  Yours sincerely,
  C. Thomas Caskey, MD, FACP
  President
  
  Ronald G. Worton, PhD, FRSC, FCCMG
  Chairman, Human Genome Committee

   

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• March 5, 1991
  C. Thomas Caskey, M.D., F.A.C.P.
  Professor and Director
  Institute for Molecular Genetics
  Baylor College of Medicine
  Houston, TX 77030
  
  Dear Tom:
  
  Thank you very much for your letter of December 28, 1990, in which you and Ron Worton, on behalf of the American Society of Human Genetics, expressed strong support for the Human Genome Project. Your letter deserved immediate response, and I apologize for the delay.
  
  I agree with the society that the biological information developed by the genome program will have a "profound impact" on our understanding of the underlying genetics of human biology and, by contributing to the understanding of the genetic basis of disease, will provide "long-term benefit . . . to human health." I am pleased that the society has stated its support in such strong terms, and I welcome the opportunity to work with you and the members of the society as the program develops. In addition to sending me your endorsement, I think it would be useful for the society to make its support and the reasons for it known to its membership and to the scientific community as a whole.
  
  As your letter included a number of specific ideas and suggestions, I would like to take this opportunity to respond to some of them. With regard to the issue of gene identification, I agree that the identification of the complete set of genes encoded within human DNA will be a major achievement of the program; I also expect many new conceptual revelations to emerge from the maps and sequence. From its beginning, the NIH genome program has considered the development of new technology for the identification of genes and other functional elements to be within its scope. I agree with the statement in your letter that the problem of identifying all of the genes in a region of DNA is, at present, a formidable task and that new techniques for gene identification are sorely needed. A similar conclusion was reached by our advisory committee, and we are therefore shortly issuing an RFA [request for applications] on "New Technologies for Detecting All Genes and Coding Regions in Genomic DNA."
  
  With respect to the next point in your letter, concerning the establishment of a standard set of a few hundred highly polymorphic markers well spaced on a reference linkage map, I am sure that you are aware that the NCHGR has announced a program to support the development of a "framework map," comprising just such markers, for each human chromosome. The grant awards for this program will be made by April 1, and our goal is to have the framework maps completed within 2-3 years. I also want to emphasize that it is integral to that program that the markers developed will be made publicly available as rapidly as possible.
  
  I am also very pleased that the ASHG recognizes the importance of the inclusion of the genomes of a variety of nonhuman organisms within the Human Genome Project. The genome program at NIH has supported the study of the genomes of important model organisms from its inception.
  
  Among the other issues addressed in your letter, I would particularly like to comment on the matter of health care delivery. The NCHGR has identified the development of standards of clinical practice and diagnostic quality control as a high priority within its program on the Ethical, Legal and Social Implications of Human Genome Research (ELSI). We are hopeful that a number of our initial activities, including both the recently funded NAS/IOM study on these issues and our work to coordinate a series of clinical pilot studies of the delivery of cystic fibrosis carrier testing, will set important precedents in this area. In addition, funding is available through the ELSI program for a variety of training workshops, short courses, demonstration programs, and educational projects designed to improve the ability of professionals to use new genetic information responsibly. You may be interested, for example, in both the summer short course that Arno Motulsky at the University of Washington is directing on these issues and the training program for genetic counselors at Northwestern University. Both of these will shortly receive NCHGR support.
  
  Thank you for your endorsement of the importance of the center's efforts to anticipate and address the ethical, legal, and social issues that the genome project could exacerbate. Our current budget plan calls for an increase of support for this area, to 4% of the center's extramural funds in fiscal year 1991 and to 5% in fiscal year 1992. We look forward to working closely with the ASHG on these issues as the program develops and welcome your ideas at any time.
  
  Finally, allow me to express my pleasure at the very effective role David Cox has played as the ASHG liaison to our Program Advisory Committee on the Human Genome. He not only attends the meetings and gives us the benefit of his advice but also participates in the working groups. From my perspective, the arrangement has been most successful.
  
  Sincerely yours,
  
  James D. Watson Ph.D.
  Director
  National Center for Human Genome Research

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