Genetics and Health Health Article

THE HUMAN GENOME PROJECT ELSI PROGRAM

One of the distinctive and important features of the Human Genome Project is its Ethical, Legal, and Social Implications (ELSI) program. James Watson committed a part of the annual appropriation from Congress to such matters from the start of the project. Three major categories of issues that have been examined in conferences, workshops, commissioned papers, and surveys are fairness, privacy, and safety.

Fairness. In the use of genetic information, fairness is especially important in preventing discrimination in access to affordable health care and life insurance and in employment. Many Americans fear genetic testing will identify a predisposition that will be (unfairly) considered a "preexisting condition" by insurance companies. As a result, genetic counselors advise that patients and families have good insurance in place before seeking counseling and testing. Even so, many individuals seek to be tested anonymously.

Privacy. Medical records and insurance health exams are not secure. In the state of Michigan, a 1999 report from the Governor's Commission on Genetic Privacy and Progress led to enactment of seven model statutes in 2000. Federal legislation is pending.

Safety and Efficacy of the Tests. Many new tests emerging from research labs need to be converted to high throughput, less expensive methods, with reliable quality-assurance programs. In general, people will be tested only once, and the test results carry implications for relatives. Autonomy of the individual has been the explicit policy for genetic counseling and informed participation in genetic screening for many years; testing must be conducted with similar respect for individual preferences and decisions.

SIGNIFICANCE OF GENETICS IN PUBLIC HEALTH

The sequencing of the human genome and the subsequent demonstration of variation in numerous genes in health and disease will surely stimulate a golden age for the public health sciences. It will be essential to investigate and link data about microbial, chemical, and physical exposures; about nutrition, metabolism, growth, and development; about lifestyle behaviors; and about diagnoses, medications, and health care utilization to information about genetic variation. Such studies must be conducted on a population basis in order to interpret the significance of the genetic variation. Laboratory scientists, clinician-investigators, and health care professionals will rely upon epidemiologists, biostatisticians, environmental health scientists, behavioral scientists, health economists, and health-policy analysts for the collaborative research that will inform evidence-based, cost-effective medical care and public health interventions.

In research, practice, and policy, both genetics and public health focus on populations. Both are interested in clinical preventive services and in prevention of environmental and behavioral risks. Both fields explicitly recognize cultural, societal, ethnic, and racial contexts. Geneticists are particularly sensitive to the legacy of the eugenics movement of several decades ago and to the conundrum of making medical decisions when no treatment or preventive intervention is yet known. So long as the United States lacks universal health insurance, discriminatory use of genetic information by insurers and by employers must be guarded against, as noted above.

More knowledge is needed about the heterogeneity of genetic predispositions, environmental exposures, and disease risks. Unfortunately, most public health research on infectious disease and environmental chemical risks has paid little attention to inherited susceptibility in people, focusing only on the environmental-disease agents. Similarly, heterogeneity of study populations has often been neglected in epidemiologic studies in the effort to generate sufficient numbers to justify the analysis statistically. For quantitative traits, pharmacologists, toxicologists, and psychologists have generally emphasized means and standard errors of the means, and neglected potentially informative people with values outside two standard deviations from the mean. Nevertheless, genetics is now at the core of research on cancers, coronary heart disease, high blood pressure, neurological and psychiatric conditions, and a host of other common conditions.

Complete genome sequences are now available for Mycobacterium tuberculosis, HIV, and hepatitis B virus; sequences will soon be available for cholera, malaria, and other agents. The ability to promptly identify disease-causing strains of these infectious agents has been a boon to epidemiologic surveillance in the community and to clinical management of patients. Genetic variation in both the agents and exposed persons interact. For both HIV and malaria, there are cell-surface variants of blood cells in humans that protect some people from infection. These host-parasite relationships will be a fertile area for new knowledge in public health and for drug development.

Nutrition and genetics interact extensively. Individuals with similar elevated levels of cholesterol have a variety of underlying conditions for which different dietary and pharmacologic approaches are needed. Another important risk factor for coronary heart disease is the amino acid homocysteine, whose level is greatly influenced by folic acids and vitamins B12 and B6, as well as genetic variation in enzymes metabolizing these vitamins. One common disorder, hereditary hemochromatosis, results from an overload of iron from the diet, leading to damage from iron deposition in the heart, liver, pancreas (diabetes), testes (infertility), skin, and joints (arthritis). Simple blood donation can reduce iron burdens in the body and prevent these serious complications. It is easy to test for elevated iron levels and for the gene mutations that predispose to the retention of excess iron. Unfortunately, the American Red Cross refuses to accept blood from these otherwise normal potential donors, and the Centers for Disease Control has been extremely cautious about undertaking screening programs on a population basis.

In the arena of environmental health, variation in susceptibility has been recognized as one of the three key components in assessment of risks, together with the dose-response relationship and the levels of exposure in relevant settings. The U.S. government has mounted an Environmental Genome Initiative to direct emerging knowledge of genes and genetic variation from the Human Genome Project and develop powerful new methods of chip technology for testing lots of genes simultaneously as an aid in identifying and preventing health risks from environmental exposures.

Across all of these fields, genetics will surely contribute to a scientifically sound strategy for improving health, preventing disease, and reducing disparities, the overarching missions of public health.

GILBERT S. OMENN

(SEE ALSO: Autonomy; Environmental Determinants of Health; Eugenics; Genes; Genetic Disorders; Human Genome Project; Medical Genetics; Nutrition; Retrovirus; and articles on specific diseases mentioned herein)