Ethics and Research Assessing the Relative Roles of Genes and the Environment*

Abstract

Research on the interaction of genes and the environment is revealing that many human diseases have both genetic and environmental components. Even traditional “environmental” diseases, such as infections, appear to interact with genetic components in the human host. Environmental genetics research will inevitably increase understanding of individual susceptibilities to toxic exposures in the environment and harmful side effects of medications; therefore, it has great promise for improving the prevention and treatment of human diseases. However, realizing the benefits of this research requires careful attention to ethical issues that are particularly relevant in this context. This article reviews some of the most pressing issues related to research design and methods, as well as from the application of research results (e.g., workplace genetic screening and legal toxic torts, personal medical responsibility, and the relationship between genetics and public health measures).

Keywords:

• environmental genetics
• ethics
• population genetics
• genetic research
• research subjects
• research standards

ACKNOWLEDGEMENTS

The authors benefited greatly from the insightful comments of Lauren Dame, JD, and four anonymous reviewers from Accountability in Research on an earlier version of this manuscript.

Matthew DeCamp's work on this manuscript was made possible by a grant from the National Institutes of Health, Medical Scientist Training Program (T32 GM07171–29). Jeremy Sugarman's work on this manuscript was made possible by a grant from the Department of Energy, “Accessible Genetics Research Ethics Education (AGREE): A Web-Based Program for IRBs and Investigators”. This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02–04ER6736.

Editor's Note: This review is an accompaniment to two articles recently published inAccountability in Research on population-based genetics research and behavioral genetics.

Notes

1 Genetic information will eventually form a substantial portion of the Human Genome Epidemiology Network, or HuGENet (Khoury, Little, and Burke 2003). HuGENet is a global collaboration for assessing and disseminating information regarding the genome's impact on health and disease. For more details, see www.cdc.gov/genomics/hugenet/default.htm. Accessed June 2004.

2 For more information, see www.niehs.nih.gov/envgenom/home.htm. Accessed June 2004. Phase 1 of the EGP is now complete, and a summary report, “Genetic Variation and Gene Environment Interaction in Human Health and Disease” (April 16, 2003), is available at www.niehs.nih.gov/envgenom/gesymp03.pdf. Accessed June 2004. The EGP has an Ethical, Legal and Social Implications (ELSI) program. A major focus of this work is on pharmacogenomics. (Pharmacogenomics is differentiated from pharmacogenetics by its focus on genome analysis, as opposed to pharmacogenetics’ focus on single genes. However, these terms are not fixed in the literature; therefore, we use the more inclusive “pharmacogenomics” and allow pharmacogenetics to be one subset of pharmacogenomics.) One reason for this may be a belief that pharmacogenomics and pharmacogenetics will be the first successful applications of environmental genetics research.

3 For one example, see www.genovations.com. Accessed June 2004.

4 A related form of research not described in this module is intentional human dosing studies. In these studies, participants are exposed to toxins, such as pesticides, to help determine appropriate safety standards. Here a set of critical questions must be addressed regarding the acceptability of exposing participants to harmful substances without offsetting personal benefit for the sake of science.

5 For one example, see First Genetic Trust's Dynamic Informed Consent at www.firstgenetic.com/products_icf.html. Accessed June 2004.

6 For more information on the volume of useful research produced by the Nurses’ Health Study, see Colditz et al. (1993) and www.channing.harvard.edu/nhs/. Accessed June 2004.

7 See also nationalchildrensstudy.gov/. Accessed June 2004.

8 See www.framingham.com/heart/. Accessed June 2004.

9 For more information, see nationalchildrensstudy.gov/news/assembly_ meeting_112003.cfm. Accessed June 2004.

10 For example, would a large-scale epidemiology study involving detailed examination of a child's physical and social environments with psychological tests and surveys, in addition to genetic information, be considered “minimal risk” (taking into account physical, psychological, economic, and social risks)? This categorization is important, because it determines whether a study can be done, and if so, what protections are necessary for the children in the study (45 CFR 46 Subpart D). “Minimal risk,” as defined in these regulations, means “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” (45 CFR 46.102i). Might environmental genetics research involve more than minimal risk? US regulations also permit studies that involve “greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition” (45 CFR 46.406). Importantly, the idea of a “condition” may extend beyond traditional disease categories to include poverty, infancy, or even a genetic predisposition to future illness. Will children in particular environments qualify as having a “condition”, or will the risks be relative to healthy children? For more information on the federal regulations in this area, see the National Human Research Protection Advisory Committee report, Clarifying Specific Portion of 45 CFR 46 Subpart D that Governs Children's Research (May 2003), online at ohrp.osophs.dhhs.gov/nhrpac/documents/nhrpac16.pdf. Accessed June 2004.

11 See www.nitromed.com/BiDil.shtml. Accessed June 2004.