Chapters in this Book
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Part I GENETICS AND PUBLIC HEALTH: AN OVERVIEW Chapter 1
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Genetics and Public Health in the 21st Century
Genetics and Public Health: A Framework for the Integration of Human Genetics into Public Health Practice
Muin J. Khoury1, Wylie Burke2, Elizabeth Thomson3
1Office of Genomics and Disease Prevention, Centers for Disease Control and Prevention, 4770 Buford Hwy, MS K28, Atlanta, GA 30341
2Department of Medicine, University of Washington, Seattle, WA 98105
3 Ethical, Legal, and Social Implications Research Program, National Human Genome Research Institute, Bethesda, MD 20892
Portions of this chapter are based on the Centers for Disease Control and Prevention’s “Translating Advances in Human Genetics into Public Health Action: A Strategic Plan” (1997) (11).
As we enter the 21st century, health care is undergoing phenomenal changes driven, in part, by the Human Genome Project and accompanying advances in human genetics (1). All of the 50,000 to 100,000 human genes will be identified in the next few years (2). As of 1999, more than 10,000 genes have been discovered and catalogued (3). Tests for more than 600 gene variants are already available in medical practice (4). Gene variants found thus far include not only those associated with rare diseases, but those that increase susceptibility to common chronic diseases, such as cancer and heart disease (5).
(Table 1). Risks for almost all human diseases result from the interactions between inherited gene variants and environmental factors, including chemical, physical, and infectious agents and behavioral or nutritional factors, raising the possibility of targeting disease prevention and health promotion efforts to individuals at high risk because of their genetic makeup (6).
Need for Public Health Leadership in Genetics
How to use knowledge from genetics research to promote health and prevent disease-the fundamental mission of public health-is now being explored. However, population-based information is lacking about the distribution of genotypes in different populations, the benefits and risks of genetic testing, and the efficacy of early interventions. Moreover, the complex issues that have emerged (e.g., rapid commercialization of genetic tests, quality of laboratory testing, availability of and access to interventions, and potential discrimination against and stigmatization of individuals and groups) call for public health leadership.
Almost daily, gene discoveries are reported for a wide variety of human diseases (7). Unfortunately, what happens after a new gene discovery is announced is often a haphazard mixture of scientific excitement, heightened public awareness and commercial interest in developing and marketing genetic tests. This problem is exemplified by the events following the 1997 publication of an association between familial colorectal cancer in Ashkhenazi Jews and the presence of a common genetic variant in the adenomatosis polyposis coli (APC) gene (8). One example of the accompanying news coverage, a 1998 article “Genetic Defect Doubles Colon Cancer Risk”(9), stated the following:
“Researchers have found a new genetic defect present in one of every 17 American Jews that doubles a person’s colon cancer risk. This mutation is now the most common cancer-associated gene defect identified in any ethnic population. Rarely present in non-Jews, the mutation appears to be responsible for about one in four cases of inherited colon cancer in Askhenazi Jews-those of Eastern European ancestry who constitute more than 95 percent of America’s six million Jewish people. The good news is that scientists have developed a blood test, available for $200, that can detect this genetic defect. The test is advisable for everyone in the Ashkhenazim population, whether they have a family history of colon cancer or not.”
Although this study needed further confirmation, and its implications for medical practice remain far from clear, the response illustrates the mounting pressures for a rapid transition from gene discovery to integration in clinical practice, which could result in the premature development and offering of genetic tests.
This book begins to explore the growing impact of the genetics revolution on public health practice in the new millennium. Section I addresses an overview of the integration of genetics in public health, starting with an overall framework (chapter 1), followed by historical perspectives (chapter 2), opportunities provided by the human genome project (chapter 3), models of public health genetics policy development (chapter 4), and the multidisciplinary nature of genetics in public health research and education (chapter 5).
Over the last 5 years, public health agencies have begun examining how advances in human genetics can be used to prevent disease and improve the health of the population (10). For example, as CDC developed a strategic plan (11) to address both the opportunities and challenges posed by advances in human genetics on public health practice, it became clear that much of public health training, infrastructure, policy and program development has not taken genetics into consideration. Notable exceptions are newborn screening programs for metabolic diseases, birth defects surveillance systems, and programs for children with special healthcare needs. Yet, as the science of gene discovery matures, there will be an increasing role for public health in closing the gap between gene discovery and applications to prevent most, if not all, human diseases, especially adult-onset chronic diseases.
The Institute of Medicine (IOM) report on the future of public health (12) can be used as a starting point for developing a long-term strategic plan for integrating genetics into public health practice. The IOM report defined three core functions for public health agencies: assessment, policy development, and assurance. Although genetics was not mentioned specifically in this report, the substantial recommendations of this report apply to all emerging areas in public health, including genetics.
The Interface of Genetics and Public Health
In recent years, a new hybrid subspecialty of genetics and public health has emerged. Public health genetics (a term mostly used in the United States [13-14]) has been defined as the application of advances in genetics and molecular biotechnology to improving public health and preventing disease (14). Community genetics (a term mostly used in Europe ) has been defined as “a branch of genetics that has service and science components.” The service component seeks to integrate genetic services into community interventions. The science component encompasses the research needed to develop and evaluate services (15). Public health genetics and community genetics could be viewed as one and the same. Nevertheless, as we think about the broader mission of public health, namely “to fulfill society’s interest in assuring conditions in which people can be healthy” (12), there will be unavoidable integration of new genetic information into all public health programs and across all diseases, whether or not the diseases are labeled “genetic diseases.”, or the services called “genetic services”. All public health professionals, therefore, will need an increasing appreciation for integrating genetic research, policy and program development into their daily work. This is not different from the expected integration of genetics into health care in general and across the various medical subspecialties (16-17). While recognizing the need for a cadre of public health researchers and practitioners fully trained in genetics, we also believe that all public health professionals will be using advances in human genetics in research and practice. We do not particularly endorse the creation of a new public health subspecialty in genetics; rather, we encourage and emphasize the smooth integration of genetics into public health practice. Some of the distinctions between these views are shown in Table 2. Nevertheless, the reader will see various terminologies and definitions used by contributing authors to address the interface between genetics and public health.
One may wonder what is the meaning of prevention in the context of genetics and public health? Juengst (19) used the terms “genotypic prevention”-the interruption of genetic trait transmission from one generation to the next through reproductive counseling, carrier testing, prenatal diagnosis and pregnancy termination-and “phenotypic prevention”-the prevention of disease and death among people with specific genotypes (19). In its strategic plan (11), CDC clearly endorses the concept of phenotypic prevention as the strategy for public health-driven programs. Phenotypic prevention can be achieved by interrupting harmful interaction of environmental cofactors with human genetic variation or by using gene therapy to correct deficiencies in gene products.
Although public health-driven prevention may be clear-cut for adult-onset multifactorial conditions such as cancer and heart disease, its role is more problematic for early-onset, lethal single-gene conditions such as Tay Sachs disease and other severe conditions affecting children. It has been argued that an important role still exists for public health activities in prenatal diagnosis and genotypic prevention of severe or lethal conditions (20). Assurance of individuals’ and couples’ access to reproductive risk information could improve their own well-being, a goal that could be encompassed within a broad definition of health. For many couples, the availability of prenatal diagnosis provides a level of reassurance that permits them to proceed with childbearing they would otherwise forego. Assuring the availability and voluntary access to prenatal services and evaluating the impact of these services would fall within the purview of public health practice; nevertheless, while the public heath community should take an active role in promoting the use of genetic tests and services when there are proven and cost-effective interventions to prevent disease, death or disability (e.g., phenylketonuria or PKU), public health agencies cannot play a role in promoting the use of genotypic prevention as a method to improve the public’s health.
Another philosophical issue in the integration of genetics into public health is what defines a genetic condition. Geneticists often make a distinction between single-gene disorders and susceptibility genes that are disease risk factors along with other genes and environmental exposures involved in disease development. This distinction is embodied in the concept of genotype penetrance. The distinction tends to fade when one realizes that all human disease is the result of interactions between genetic variation and the environment (broadly defined to include dietary, infectious, chemical, physical and social factors). Even many of the classical single-gene metabolic disorders are the result of a deficiency in a nutritional enzyme combined with dietary exposure to one or more chemicals (e.g., phenylalanine and phenylalanine hydroxylase deficiency in PKU; and iron intake and mutations in the HFE gene in hereditary hemochromatosis (17). As Rothman puts it, “It is easy to show that 100% of any disease is environmentally determined and 100% is genetically determined as well. Any other view is based on a naive understanding of causation” (21). Perhaps the wide range of penetrance with respect to clinical disease could be due, in part, to variations in the prevalence of interacting cofactors (e.g., other genes and modifiable risk factors). Universal exposure of newborn infants to phenylalanine through their diets leads to a high incidence of mental retardation among those who inherit a deficiency in phenylalanine hydroxylase.
If we accept the fundamental premise that genetic variation is associated with all human disease, there is no compelling reason to label a disease as genetic or not. For example, one can label hereditary hemochromatosis as an iron overload disorder resulting from the interaction between an inherited variation in iron transport, iron intake and iron loss. Similarly, breast cancer in some individuals could result from the interaction between an inherited mutation in the BRCA1 gene and yet-to-be-described cofactor(s), including other genes and modifiable risk factors. When this book’s authors refer to “genetic disorders,” they are usually referring to conditions in which a single gene with high penetrance or a chromosomal abnormality have been implicated. It is implicit, however, that genetic factors do play a role in the etiology of virtually all human diseases, even those that are traditionally not thought of as “genetic” (e.g., infectious and occupational diseases).
Thus, an important theme of this book is the need to identify the modifiable risk factors for disease that interact with the genetic variation and that may be used to help target preventive interventions. Recognition of the need to apply knowledge about the interaction between environment and genetics to health care has been described in the popular press (22).
Finally, an inherent assumption in our discussion of the future of genetics in public health is that much of the delivery of genetic tests and services for disease prevention and health promotion, including adequate family history assessment and genetic counseling, will be done within the context of the broader healthcare system. Managed care organizations will play an important role in integrating genetic services into disease prevention and health promotion activities.
Framework for Integrating Genetic Discoveries into Public Health Functions
A framework for applying essential public health functions in evaluating the relevance of gene discoveries to disease prevention and health promotion was developed as part of the CDC’s strategic plan for genetics and public health (11). This framework encompasses four essential public health functions and three critical issues that affect each function (Table 3). The rest of this book is largely organized according to these public health functions and related critical issues. The following provides a brief overview.
I. The Role of Public Health Assessment in Genetics
Public health assessment in genetics relies on scientific approaches to assess the impact of discovered genes on the health of communities. The traditional forms of applied research in public health include surveillance and epidemiology, which are explored in more detail in section II (chapters 6 through 11).
In general, surveillance-the systematic gathering, analysis and dissemination of population data (23)-is needed to determine the population frequency of genetic variants that predispose people to specific diseases, both common and rare; the population frequency of morbidity and mortality associated with such diseases; and the prevalence and effects of environmental factors known to interact with given genotypes in producing disease. Information could be gathered also through broader surveillance of the economic costs of the genetic component of various diseases (e.g., expressed by healthcare costs, hospitalization rates, years of potential life lost and other measures); genetic testing issues (e.g., access to services, quality of tests, usage by providers and potential discrimination); and issues related to interventions (e.g., availability, safety and effectiveness). Examples of existing surveillance and health information systems include the National Health and Nutrition Examination Survey (24), population-based birth defects surveillance systems (25) and cancer surveillance systems (26).
Epidemiology is often viewed as the scientific core of public health. A widely used definition is “the study of the distribution and determinants of health-related states or events in populations, and the application of this study to control health problems” (27). Epidemiologists not only investigate outbreaks of disease in different populations but also conduct studies to determine risk factors for various diseases, identify high-risk subpopulations to which to target prevention and intervention actions, and evaluate the effectiveness of health programs and services in improving the population’s health (28).
Over the last two decades, epidemiologic methods and approaches have been increasingly integrated with those of genetics through the discipline of genetic epidemiology, which seeks to identify the role of genetic factors in disease occurrence in populations and families (29). In addition, a new brand of epidemiology has emerged-molecular epidemiology-that seeks to study disease occurrence using biological markers of exposure, susceptibility and effects (30).
Most discoveries for gene variants are based on studies of high-risk families or selected groups. To translate the results of this genetic research into opportunities for treating and preventing disease and promoting health, population-based epidemiologic studies are increasingly needed to quantify the impact of gene variants on the risk of disease, death and disability, and to identify and quantify the impact of modifiable risk factors that interact with gene variants. The results of such studies will help health professionals to better target medical, behavioral and environmental interventions. Epidemiologic studies are also required for clinical validation of new genetic tests, monitoring a population’s use of genetic tests, and determining the safety, effectiveness and impact of genetic tests and services in different populations.
To accomplish translation of genetic discoveries into public health practice, epidemiologists must collaborate with practitioners of other disciplines such as clinical genetics, laboratory sciences, behavioral and social sciences, communication sciences, ethics, and law. A combined genetic-epidemiologic approach is essential for better understanding disease etiology and developing molecular diagnostics. Data generated from such collaborations are urgently needed in developing medical and public health policy. For example, issues have been debated regarding population-based genetic testing for breast cancer in relation to BRCA1 (31); Alzheimer’s disease in relation to the Apolipoprotein E-E4 allele (32); and iron overload in relation to the hemochromatosis gene (33). Given the paucity of population-based epidemiologic data regarding the frequency of and disease risks and environmental interactions for many newly discovered human gene variants, there is concern that appropriate health policy on the use of genetic tests may not be possible.
Human Genome Epidemiology
The term “human genome epidemiology” (HuGE) denotes an evolving field of inquiry that systematically applies epidemiologic methods and approaches in population-based studies of the impact of human genetic variation on health and disease. HuGE can be viewed as the intersection between genetic epidemiology and molecular epidemiology (34). Whereas genetic epidemiology has traditionally focused on techniques to find disease genes using linkage and segregation analysis, and molecular epidemiology focuses on using biological markers in epidemiologic studies.
The wide spectrum of topics addressed by investigators working on human genome epidemiology and selected examples are shown in Table 4(36). The spectrum ranges from population-based epidemiologic research on gene variants to evaluation of genetic tests and services. Ultimately, HuGE represents the application of clinical and molecular research to a population setting and involves the collaboration and contribution of numerous specialties.
In 1998, a collaboration of individuals and organizations launched the Human Genome Epidemiology Network (HuGE Net). This global effort seeks to (1) promote collaboration in developing and disseminating of peer-reviewed epidemiologic information on human genes; (2) develop an updated and accessible knowledge base on the World Wide Web; and (3) promote use of this knowledge base by health care providers, researchers, industry, government, and the public for making decisions involving the use of genetic tests and services for disease prevention and health promotion (34-35).
II. Evaluation of genetic testing
The book we will focus on two main types of evaluation-related activities: (1) the assessment of how and when genetic tests can be or are used to promote health and to diagnose and prevent human disease; and (2) the development of standards and guidelines for assuring quality genetic testing. As defined by the Task Force on Genetic Testing, genetic tests include the analysis of human DNA, RNA, chromosomes, proteins, and certain metabolites in order to detect a person’s genotype for clinical purposes, including predicting risk of disease, identifying carriers, and establishing prenatal and clinical diagnosis or prognosis (37).
The Task Force on Genetic Testing recognized the need to evaluate several types of data parameters (analytic validity, clinical validity, and clinical utility as defined in Table 5) for each genetic test before transitioning the test from research to clinical practice. Since evaluation of genetic tests used in the prediction of adult-onset diseases may require years of follow up, the Task Force also outlined the need for post-market reevaluation of the same three parameters for genetic tests in the context of “real-world” use and to reevaluate policies and recommendations on the use of genetic tests. These and other parameters of the pre-analytic and post-analytic testing process need to be continuously evaluated in population-based settings.
The second main area of evaluation concerns the development of standards, regulations, and guidelines to ensure the accuracy, validity, and precision of laboratory procedures and to ensure that other quality assurance issues are addressed as well.
All clinical laboratories in the United States that provide information to referring physicians are certified under the Clinical Laboratory Improvement Act (CLIA) Amendments of 1988 (38). CLIA standards for quality control, proficiency testing, personnel, and other quality assurance practices apply to all genetic tests. CLIA regulations, which are jointly developed and administered by the Health Care Financing Administration and CDC, include additional specific requirements for cytogenetic testing. A genetics subcommittee of the CLIA Advisory Committee has considered more specific requirements for molecular genetic testing.
Another role for public health could be development of model quality assurance programs, including proficiency testing programs for genetic testing in public health programs such as the Newborn Screening Quality Assurance Program (Chapter 13). These model programs would set standards for testing, monitor the quality of testing, and recommend improvements for laboratory quality assurance.
The need for quality assurance programs in molecular genetic testing is highlighted in the results of a mail survey of 245 molecular genetic testing laboratory directors conducted by McGovern et al. (39). The researchers collected and analyzed data regarding availability of clinical molecular genetic testing, including data on personnel standards and laboratory practices.. They found a wide range of mean quality assurance (QA) scores, with 15% of the laboratories scoring lower than 70%, suggesting that both personnel qualification and laboratory practice standards are in need of improvement to ensure quality in clinical molecular genetic testing laboratories. Evaluation of genetic testing is explored in more detail in Section III (chapters 12 and 13).
III. Development, implementation, and evaluation of population interventions
The translation of advances in human genetics into actual disease prevention opportunities requires strong public health leadership in developing, implementing and evaluating disease intervention strategies. Burgeoning genetic knowledge is accompanied by high expectations that identification of genetically susceptible people will permit tailoring of prevention efforts to improve their effectiveness; yet, the clinical use of genetic information poses risks as well. Social scientists have postulated an adverse effect of genetic testing on psychological well-being and family functioning (40-41). The potential for loss of health, life or disability insurance or other discrimination as a result of genetic testing has also been raised (42). Of equal concern is that genetic tests will be used to identify persons at increased risk of disease before effective measures to reduce their risk are available. In order to formulate sound policy decisions regarding the appropriate use of genetic information in population-based testing programs, a systematic, evidence-based approach should be used to assess the potential benefits and risks of genetic testing.
Since 1968, a list of principles for population-based screening programs have been developed (43) and modified by various groups (e.g., the American College of Medical Genetics (44), and the National Academy of Sciences, ) with respect to genetic screening. More recently, Coughlin et al. have synthesized from the literature emerging elements of a set of principles on the use of genetic information in population-based adult-onset chronic disease prevention programs (46). These principles include (1) assessment of scientific evidence on the relationship between genotype, disease, and genetic test parameters (shown in Table 5); (2) systematic review of the benefits, risks and costs of screening to the target population; (3) a policy development process using consensus conferences, workshops or other approaches to evaluate the appropriateness of population testing; and (4) an evaluation process that should include various measures of access to the testing program as well as impact and effectiveness, including need for revision of testing recommendations based on new scientific evidence.
Thus, an important role of public health will be to develop intervention strategies for diseases with a genetic component, implement pilot demonstration programs and evaluate the impact of interventions on reducing morbidity and mortality in the population. Section IV contains a series of chapters that discuss needs assessment and delivery of genetic services (chapters 14 through 17), application of prevention effectiveness principles to genetics programs (chapter 18), and impact of genetic counseling on public health (chapter 19). Another series of chapters in this section illustrate the process of policy and program development and evaluation in relation to specific disease conditions, including PKU (chapter 20), cystic fibrosis (chapter 21), sickle cell disease (chapter 22), hemochromatosis (chapter 23), and coronary heart disease (chapter 24). Although much of the discussion of genetic services still focuses on traditional genetic programs related to reproductive genetics and child health, an increasing emphasis will be in the next few years on the utility of genetic testing for preventing adult-onset diseases.
IV. Communication and information dissemination
The fourth public health function in genetics is developing and applying communication principles and strategies related to advances in human genetics, the use of genetic tests and services, interventions, and the ethical, legal, and social issues related to these topics. The relevance of advances in human genetics to disease prevention and health promotion needs to be communicated to a large number of audiences, including policy makers, healthcare providers, researchers and the general public (11). Public health agencies can play a crucial role in translating the ever-growing, amount of complex information related to genetics and disease prevention to healthcare providers and communities alike. Early on, the public health community needs to develop a baseline understanding of both professional and consumer perceptions of and attitudes toward the recent developments in and future expectations for human genetics. Because the subject of human genetics can be sensitive, effective communication will be key to the success of public health programs involving genetic research results. Effective communication could be achieved by coalition building among federal agencies, professional organizations, consumers, private industry, and state and local health departments to develop and evaluate communication strategies for genetics and public health. Communication effectiveness will hinge on many factors, including coordinating communication strategies among various groups; targeting appropriate audiences with messages that result in health promotion and disease prevention; and providing messages that are accurate and appropriate on technical and cultural levels. Particular attention must be given to primary care physicians, nurses, and other health professionals who will often serve as a conduit for information and who can help shape widespread attitudes and behaviors. Finally, an appropriate mix of mechanisms should be used for disseminating information, including distance-based interactive meetings, information centers and means of electronic communication (e.g., the Internet). Chapter 28 discusses overall principles of communication science related to genetics and public health and focuses on the Internet as an emerging medium for information dissemination (chapter 31).
In order to integrate genetics into the four public health functions discussed (public health assessment, genetic testing evaluation, public health intervention, and communication), three critical issues must be addressed for each: partnerships and coordination; ethical, legal and social implications (or issues); and education and training. Details on these critical issues are provided in the CDC strategic plan on genetics and public health (11). Section V (chapters 25 through 27) addresses some of the emerging ethical and legal issues related to the integrating genetics into public health practice. Section VI other critical issues such as training public health professionals in genetics (chapter 29), and consumer and public perspectives on genetic testing (chapter 30).
The following are highlights of these topics.
I. Partnerships and coordination
For all of the public health functions in genetics discussed earlier to be carried out, strong partnerships and coordination of efforts among various groups need to occur (11), including partnerships and coordinated efforts among various agencies of the federal government; federal, state and local agencies; the public and private sectors; and the public health, medicine and academic sectors, with various community and consumer involvement.
One example of such partnership is annual national meetings on genetics and public health. CDC, the Health Resources and Services Administration (HRSA), the National Human Genome Research Institute, and the Association of State and Territorial Health Officials (ASTHO) and affiliates held the First Annual Conference on Genetics and Public Health in Atlanta, Georgia, in May of 1998 (47). This first meeting addressed the public health opportunities and challenges presented by advances in human genetics research. The conference sought to establish awareness about the scope of and process for integrating advances in human genetics into public health programs and strengthening partnerships for disease prevention and health promotion efforts. The conference was attended by nearly 400 people from federal, state, academic, consumer, community, and industry organizations, representing 41 states and several European countries. The second annual meeting in December, 1999, is cosponsored by ASTHO in collaboration with the Maryland Department of Health and Johns Hopkins University School of Hygiene and Public Health. These meetings will provide crucial gatherings for exchanging information and building partnerships among various groups.
II. Ethical, Legal and Social Issues
As the Human Genome Project was being planned, there was widespread recognition that the information gained from sequencing the human genome would have profound implications for individuals, families and society. A number of complex ethical, legal and social issues can arise around the integration of genetic technologies in practice, and the use and interpretation of genetic information. To address these issues, the Ethical, Legal and Social Implications (ELSI) Program was established as an integral part of the Human Genome Project (48-49). The program has provided leadership in scientific research by identifying, analyzing and addressing the ethical, legal and social implications of human genetics research as basic scientific discoveries were made. The overarching aims of the ELSI Program have been to assure that: (a) genetic research is conducted in an ethically sound manner; (b) genetic technologies and information are appropriated integrated into clinical and non-clinical settings; (c) genetic information is interpreted accurately and used appropriately; and (d) professionals and the public become more “genetically literate.”
Over the past decade, emphasis has been placed on privacy and fairness in the use and interpretation of genetic information. Privacy and fairness issues include (a) privacy and confidentiality of genetic information, including issues of ownership and control of genetic information and consent to disclosure and use of genetic information; (b) fair use of genetic information (e.g., related to insurance and employment); (c) individual, family and group psychological interactions and stigmatization related to genetic information; (d) cultural differences in the uses of genetic information; and (e) the impact of genetic information on the concept of disability (48).
Another ELSI research emphasis has been addressing issues related to genetic research, particularly research in which the risks and benefits to participants is not fully known. Specific topics in this area have included the elements of informed consent for individuals participating in genetics research; the role of institutional review boards in genetics research; policies related to effectively maintaining privacy and confidentiality of genetic information about individuals and families participating in genetics research; and issues raised by commercialization of the products from human genetics research (e.g., ownership of tissue and products, patents, etc..).
While much of ELSI research has been driven by concerns about the human rights of individuals and their families in the context of genetic testing for single-gene disorders with relatively high penetrance (e.g., mutations conferring cancer predisposition), the interface between ELSI and public health practice (or PHELSI) leads to a set of concerns that are somewhat different from the traditional clinical practice involving genetic testing and counseling of high-risk families (Table 6). Section V addresses some but not all of these issues, including the interface between public health and the law (chapter 25), the informed consent process in traditional public health genetics programs (chapter 26), and issues surrounding public health surveillance and information systems (chapter 27). At this time, many of these issues are unresolved. Public health leadership is needed be ensure discussion of sensitive issues and consensus building that balances individual rights with societal concerns, and they highlight an urgent need for population-based epidemiologic research.
One issue that has received a lot of attention over the past decade is the informed consent process for using stored genetic research tissue samples (50-2). In a public health setting, stored samples from large-scale national surveys or newborn blood spots could be used to conduct human genome epidemiologic studies for evaluating the impact of genetic variation on the burden of disease in the population. Although there is universal agreement on the need to obtain informed consent from subjects participating in genetic research, opinions differ regarding the use of stored samples from population surveys for which there is no or inadequate informed consent. There has been debate about the practicality of recontacting subjects from population studies; whether or not genetic studies pose more than “minimal risks” to subjects; the definitions and desirability of “anonymization” of existing samples; and whether or not coded but “linked” or “linkable” samples can be used (e.g., 50) (Table 6).
In these discussions, a distinction has been made between allelic variants that have high penetrance or risk for disease and the more common genetic variants (e.g., blood groups, HLA antigens, variants in drug metabolizing enzymes) that are neither necessary nor sufficient for disease development (50, 53-5). The latter group of genetic variants are risk factors that act in combination with other genes and environmental factors and are often associated with low relative risks for disease; however, in most existing recommendations and guidelines put out by various groups, the distinction between the two types of genetic variation has not been considered, perhaps implying that all genetic testing should be treated the same with respect to potential harm to individuals. Currently, the National Bioethics Advisory Commission, appointed by the President of the United States, has deliberated on genetic research on stored tissue samples (56). As recommendations on informed consent issues are developed by various groups, it is obvious that public health officials and researchers need to work with clinicians, ethicists, social scientists, lawyers, consumers and other groups, and to participate through individual action and through professional organizations, in defining and resolving these issues for public health practice.
III. Education and Training
The rapid expansion of the field of human genetics strains the ability of public health researchers, health practitioners, policy makers, and consumers to keep abreast of new information and its potential ramifications for policy, research and practice; therefore, concerted efforts are needed to provide various audiences, especially public health professionals, with the knowledge and skills they need to integrate genetics into public health activities. This emphasis on training public health professionals is exemplified by ongoing CDC training activities (57) as well as the development of several genetics training programs in various U.S. schools of public health. An overview of such efforts is given in Chapter 29.
There have been other national efforts to address education of professionals in various health disciplines other than public health in genetics. In 1996, the American Medical Association, the American Nurses Association, and the National Human Genome Research Institute formed the National Coalition for Health Professional Education in Genetics (NCHPEG) to promote health professional education and access to information about advances in human genetics (1). NCHPEG is a multidisciplinary group of leaders from more than 100 diverse health professional organizations, consumer and voluntary groups, government agencies, private industry, managed care organizations, and genetics professional societies.
To accelerate training in genetics for public health professionals, the content of existing courses will have to be supplemented by revised curricula or course work For example, training for laboratory personnel will need to cover new genetic tests and reagents and may result in recertification of these professionals. Training modules that address each component of the proposed framework (public health assessment, genetic testing evaluation, intervention, and communication) will need to be incorporated into the training of professionals in various public health disciplines (e.g., epidemiology, biostatistics, behavioral and social sciences, health services research, economics, health policy and management, and environmental health). A minimum level of competence needs to be achieved not only in genetics and disease prevention but in the ethical, legal, and social issues related to it.
Members of the general public will need to be similarly educated to become informed consumers of medical and genetic services and to be aware of potential misuse of genetic information. In addition, incorporating information on genetics into the life science curricula of elementary and secondary schools will help prepare the next generation to be responsive to the challenges and opportunities of genetic technology.
With acceleration of the discovery of human genetic variation and associated diseases in the next few years, public health professionals will not only be confronted with but will help develop, analyze and disseminate a large body of scientific information that will guide public health action. The potential for inappropriate or premature use of genetic information without adequate protections for privacy and confidentiality will demand public health leadership in evaluating and resolving the many ethical, legal and social issues associated with genetic information. In the not too distant future, however, disease prevention and health promotion programs will routinely consider whether or not to use genetic information to help target intervention activities in order to maximize benefit and minimize costs and harm to individuals. For this to occur, however, genetics needs to be incorporated into training programs for numerous fields (e.g., epidemiology, laboratory sciences, legislation and policy, medicine, nursing, behavioral and social sciences and communication sciences). This will require changes in professional training programs and targeted retraining of many public health professionals. Only then can we achieve a true integration of human genetics into public health practice in the 21st century.
*Includes identified or mapped genes.
Source: Online Mendelian Inheritance in Man [database] (1999) (3).
Source: Adapted from CDC (1997) (11).
Source: Holtzman and Watson (1997) (37).
I. Informed consent in public health genetic research
How can truly informed consent for genetic testing be obtained in public health practice (versus clinical practice, in which personal contact and the opportunity for one-on-one interaction is greater)?
How does informed consent for genetic testing in public health practice differ from informed consent for other public health services?
Should genetic counseling services be provided as part of public health practice even when risks associated with different genetic polymorphisms and mutations vary widely? And how can such services be provided?
How can stored samples on large scale populations (e.g., newborn screening blood spots) be used for epidemiologic research?
Under what circumstances is new consent for archived specimens needed for public health investigations?
Under what circumstances, if any, is it appropriate to make specimens anonymous?
Do situations occur in public health when genetic testing could be done on identifiable specimens without informed consent?
II. Legal issues for public health genetics programs
Should genetic programs in the public health setting be mandated by law?
What legal protections can be used to ensure confidentiality to persons participating in screening programs?
What laws and regulations are needed to ensure the safety and effectiveness of genetic tests?
III. Population access to clinical and preventive services
How can population access to genetic tests and services be ensured?
IV. Privacy concerns in population-based surveillance programs
How can privacy and confidentiality be maintained in the public health setting?
How should population-based disease registries be handled? What are their immediate and long-term benefits? What are their immediate and long-term risks?
How can public health agencies maximize benefits and minimize the risks associated with such registries?
V. Group stigmatization
How can concerns about potential stigmatization of population groups that result from research or testing programs be addressed?
Source: CDC (1997) (11).
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