What Research Ethics Should Learn from Genomics and Society Research: Lessons from the ELSI Congress of 2011

The “2011 ELSI Congress: Expanding the ELSI Universe” was held in Chapel Hill, NC, from April 12–14, hosted by the Center for Genomics and Society at the University of North Carolina at Chapel Hill, an NHGRI-funded Center of Excellence in ELSI Research (P50 HG004488, Gail Henderson, PI). The Congress was funded by a supplement to this center grant. Other sponsors included the Carolina Center for Genome Sciences; the UNC School of Medicine, Department of Social Medicine; the UNC Center for Bioethics; the Wake Forest University Center for Bioethics, Health and Society; and the North Carolina Translational and Clinical Sciences Institute.

In the fall of 2003, the NHGRI in collaboration with U.S. Department of Energy (DOE) and the National Institute of Child Health and Human Development (NICHD) launched a new initiative to create interdisciplinary Centers of Excellence in ELSI Research (CEER). The CEERs are designed to bring investigators from multiple disciplines together to work in innovative ways to address important new, or particularly persistent, ethical, legal, and social issues related to advances in genetics and genomics. In addition, the centers will support the growth of the next generation of researchers on the ethical, legal and social implications of genomic research. Special efforts will be made to recruit potential researchers from under-represented groups. See <http://www.genome.gov/ELSI/#al-4> (last visited December 7, 2012).

In January, 1990, the ELSI Working Group issued its first report and defined the function and purpose of the ELSI program as follows: “1. To anticipate and address the implications for individuals and society of mapping and sequencing the human genome; 2. To examine the ethical, legal and social consequences of mapping and sequencing the human genome; 3. To stimulate public discussion of the issues; 4. To develop policy options that would assure that the information be used to benefit individuals and society.” The ELSI Working Group envisioned a program that would anticipate problems and identify possible solutions and suggested a number of means to accomplish these goals. Specifically, it encouraged the research community to explore and gather data on a wide range of issues pertinent to the Human Genome Project that could be used to develop education programs, policy recommendations or possible legislative solutions. A number of focus areas were identified, including: fairness in the use of genetic information; the impact of knowledge of genetic variation on individuals; and privacy and confidentiality of genetic information. See <https://www.genome.gov/10001754#al-2accessed12/14/2012> (last visited December 14, 2012).

The Planning Committee was composed of ELSI researchers, both CEER and non-CEER affiliated. It also included two individuals from outside the U.S. and members of the ELSI program staff. The following were members: Bernhardt Barbara Boyer Joy Caulfield Tim Chung Wendy Cook-Deegan Bob Goldenberg Aaron Henderson Gail Juengst Eric Kaye Jane King Nancy Lee Sandra McEwen Jean Press Nancy Royal Charmaine Thomson Elizabeth , and Van Riper Marcia .

Volunteer note takers for the Congress included: Ertola Astrid Cunningham Brooke Caga-Anan Charlisse Brewer Cheryl Clarke Colleen Lassiter Dragana Guzaukas Greg Peace Jane Erickson Jessica Yu Joon-Ho Sutton Karey West Kate McGlone Maxson Kathryn Byerly Katie Hogan Kelly Shutske Krysta Wagner Laura Milner Lauren Sayres Lauryn Jamal Leila Barata Llida Michie Marsha King Martha Allyse Megan Easter Michele Montgomery Michelle Garrison Nanibaaa' Haase Rachel Knerr Sarah Smolek Sondra Tuteja-Stevens Sony , and Fortson Wendell .

On February 10, 2011, Nature magazine published NHGRI's strategic plan for the future of human genome research: “Charting a course for genomic medicine from base pairs to bedside.” This plan includes a section on Genomics and Society that outlines four areas that will need to be addressed as genomic science and medicine move forward. Based on these areas, the NHGRI has developed the following broad research priorities: 1. Genomic Research. The issues that arise in the design and conduct of genomic research, particularly as it increasingly involves the production, analysis and broad sharing of individual genomic information that is frequently coupled with detailed health information. 2. Genomic Health Care. How rapid advances in genomic technologies and the availability of increasing amounts of genomic information influence how health care is provided and how it affects the health of individuals, families and communities. 3. Broader Societal Issues. The normative underpinnings of beliefs, practices and policies regarding genomic information and technologies, as well as the implications of genomics for how we conceptualize and understand such issues as health, disease, and individual responsibility. 4. Legal, Regulatory and Public Policy Issues. The effects of existing genomic research, health and public policies and regulations and the development of new policies and regulatory approaches. See <http://www.genome.gov/10001618#al-2> (last visited December 7, 2012).

Appelbaum and colleagues coined the term “therapeutic misconception” in 1982. Appelbaum P. S. Roth L.H. , and Lidz C. , “The Therapeutic Misconception: Informed Consent in Psychiatric Research,” International Journal of Law and Psychiatry 5, No. 3-4(1982): 319–329. See also subsequent work on assessment of informed consent, perceptions of benefit in research, and the therapeutic misconception: Appelbaum P. S. Roth L. H. Lidz C. W. Benson P. , and Winslade W. , “False Hopes and Best Data: Consent to Research and the Therapeutic Misconception,” Hastings Center Report 17, no. 2 (1987): 20–24; King N. M. P. , “Defining and Describing Benefit Appropriately in Clinical Trials,” Journal of Law, Medicine & Ethics 28, no. 4 (2000): 332–343; Miller M. , “Phase I Cancer Trials: A Collusion of Misunderstanding,” Hastings Center Report 30, no. 4 (2000): 34–43; Joffe S. and Weeks J. C. , “Views of American Oncologists about the Purposes of Clinical Trials,” Journal of the National Cancer Institute 94, no. 24 (2002): 1847–1853; Dresser R. , “The Ubiquity and Utility of the Therapeutic Misconception,” Social Philosophy and Policy 19, (2002): 271–294; Horng S. and Grady C. , “Misunderstanding in Clinical Research: Distinguishing Therapeutic Misconception, Therapeutic Misestimation, and Therapeutic Optimism,” IRB 25, no. 1 (2003): 11–16; Sankar P. , “Communication and Miscommunication in Informed Consent to Research,” Medical Anthropology Quarterly 18, no. 4 (2004): 429–446; Brody B. A. McCullough L. B. , and Sharp R. R. , “Consensus and Controversy in Clinical Research Ethics,” JAMA 294, no. 11 (2005): 1411–1414; Miller F. G. and Joffe S. , “Evaluating the Therapeutic Misconception,” Kennedy Institute of Ethics Journal 16, no. 4 (2006): 353–366; Appelbaum P. S. and Lidz C. , “Re-evaluating the Therapeutic Misconception: Response to Miller and Joffe,” Kennedy Institute of Ethics Journal 16, no. 4 (2006): 367–373.

See, e.g., Jansen L. A. , “A Closer Look at the Bad Deal Trial: Beyond Clinical Equipoise,” Hastings Center Report 35, no. 5 (2005): 29–36; Largent E. A. Joffe S. , and Miller F. G. , “Can Research and Care Be Ethically Integrated?” Hastings Center Report 41, no. 4 (2011): 37–46. 9. The following articles present findings from a study (R01 HG 02087, Gail Henderson, PI) of perceptions of benefit in gene transfer trials: Churchill L. R. Nelson D. K. , and Henderson G. E. , “Assessing Benefits in Clinical Research: Why Diversity in Benefit Assessment Can Be Risky,” IRB: Ethics and Human Research 25, no. 3 (2003): 1–8; Henderson G. E. Davis A. M. King N. M. P. , “Uncertain Benefit: Investigators' Views and Communications in Early Phase Gene Transfer Trials,” Molecular Therapy 10, no. 2 (2004): 225–231; King N. M. P. Henderson G. E. , and Churchill L. R. , “Consent Forms and the Therapeutic Misconception: The Example of Gene Transfer Research,” IRB: Ethics and Human Research 27, no. 1 (2005): 1–8; Henderson G. E. Easter M. E. , and Zimmer C. R. , “Therapeutic Misconception in Early Phase Gene Transfer Trials,” Social Science and Medicine 62, no. 1 (2006): 239–53; Henderson G. E. Churchill L. R. , and Davis A. M. , “Clinical Trials and Medical Care: Defining the Therapeutic Misconception,” Public Library of Science-Medicine 4, no. 11 (2007): 1735–1738.

See, for example, Wolf S. M. and colleagues, “Managing Incidental Findings in Human Subjects Research: Analysis and Recommendations,” Journal of Law, Medicine & Ethics 38, no. 2 (2008): 216–435. Wolf has argued that clinical researchers have an obligation to return incidental findings, while Clayton E. , among others, has argued for caution; see Clayton E. W. , “Incidental Findings in Genetics Research Using Archived DNA,” Journal of Law, Medicine & Ethics 38, no. 2 (2008): 286–291.

NHGRI issued a press release on September 26, 2011, announcing seven grants awarded under a new call for research on return of results in genomic research:

The National Human Genome Research Institute (NHGRI) today awarded seven grants, totaling $5.7 million, aimed at untangling one of the knottiest ethical issues facing genomic researchers. Under the microscope are issues around if, when and how researchers should return to study participants information about their risk for diseases or conditions discovered during studies of their genomes… Researchers have widely varying opinions on the ‘return of results’ issue. Some believe that they have an ethical or legal obligation to reveal to study participants their genomic information – especially if it is medically significant and interventions can prevent or reduce the risk of a disorder. Others consider sharing such information unethical – especially if the research participant was told he or she would not be re-contacted, if the information relates to a disorder for which there is no known intervention, or if the precise medical significance of the information is unclear. Researchers on both sides of the question must also consider regulatory and policy issues related to bringing genome sequencing to clinical applications. Until now, researchers have had very little data to guide their decisions, except for research that asks people hypothetically whether they want incidental findings returned to them. An incidental finding is a health finding about a research participant that is discovered in the course of conducting research but is not the central aim of the study. What people want in the abstract may be very different from what they want in an actual genomic research setting. See <http://www.genome.gov/27545526> (last visited December 7, 2012). On December 6, 2011, they issued a press release for Clinical Sequencing Exploratory Research Projects. To help speed up the application of genomic science to medical care, NHGRI will invest $40 million over four years to support five Clinical Sequencing Exploratory Research Projects, in which new multi-disciplinary research teams will explore the ways in which healthcare professionals may use genome sequencing information in a medical care setting. Physicians, ethicists, genomic scientists, patients and families will work together to learn important lessons about the use of genome sequencing in medical care and to develop methods to improve its use in the future…Clinical Exploratory Research Projects will answer questions such as how to incorporate genomic data into medical records, what tools are needed to extract relevant information from a patient's genome sequence, and how the availability of genome sequence data affects a physician's recommendations regarding treatment. The research will include important ethical and psycho-social elements, such as how patients should be counseled and educated before having their genome analyzed, the best way to acquire patient consent to participate in a study, and when to return findings to patients that are not related to the primary medical condition for which the test was done. The program will also provide a forum for the development and dissemination of innovative and best practices for clinical genome sequencing. At <http://www.nih.gov/news/health/dec2011/nhgri-06.htm> (last visited December 7, 2012).

Bailey D. B. Jr. Skinner D. Davis A. M. Whitmarsh I. , and Powell C. , “Ethical, Legal, and Social Concerns about Expanded Newborn Screening: Fragile X Syndrome as a Prototype for Emerging Issues,” Pediatrics 121, no. 3 (2008): e693–e704; Bailey D. B. Jr. Skinner D. , and Warren S. F. , “Newborn Screening for Developmental Disabilities: Reframing Presumptive Benefit,” American Journal of 'Public Health 95, no. 11 (2005): 1889–1893; Grosse S. D. Boyle C. A. , and Kenneson A. , “From Public Health Emergency to Public Health Service: The Implications of Evolving Criteria for Newborn Screening Panels,” Pediatrics 117, no. 3 (2006): 923–929; Ross L. F. , Research Review, “Screening for Conditions That Do Not Meet the Wilson and Jungner Criteria: The Case of Duchenne Muscular Dystrophy,” American Journal of Medical Genetics 140A, no. 8 (2006): 914–922.

Juengst E. , “Metagenomic Metaphors: New Images of the Human from ‘Translational’ Genomic Research,” in Drenthen M. Keulartz J. , and Proctor J. , eds., New Visions of Nature: Complexity and Authenticity (New York: Springer, 2009): 128–153.

Burchard E. Ziv E. , and Coyle N. , “The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice,” New England Journal of Medicine 348, no. 12 (2003): 1170–1175; Cooper R. Kaufman J. , and Ward R. , “Race and Genomics,” New England Journal of Medicine 348, no. 12 (2003): 1166; Foster M. W. and Sharp R. R. , “Race, Ethnicity, and Genomics: Social Classifications as Proxies of Biological Heterogeneity,” Genome Research 12, no. 6 (2002): 844–850; Lee S. S. Mountain J. , and Koenig B. , Open Letter, “The Ethics of Characterizing Difference: Guiding Principles on Using Racial Categories in Human Genetics,” Genome Biology 9, no. 7 (2008): 404; Ossorio P. and Duster T. , “Race and Genetics: Controversies in Biomedical, Behavioral, and Forensic Sciences,” American Psychologist 60, no. 1 (2005): 115–128; The Race, Ethnicity, and Genetics Working Group, National Human Genome Research Institute, “The Use of Racial, Ethnic, and Ancestral Categories in Human Genetics Research,” American Journal of Human Genetics 77, no. 4 (2005): 519–532.

See the Institute of Medicine volume which documents the impacts of uncertainty on racial stereotyping in clinical care. Smedley B. D. Stith A. Y. , and Nelson A. R. , eds., Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care (Washington, D.C.: National Academies Press, 2003).

A phrase coined by Eric Juengst to illustrate our point on behalf of the Center for Genetic Research Ethics and Law (CGREAL) at Case Western Reserve University. Juengst E. , NIH Grant Application # 2 P50-HG003390–06, “Center for Genetic Research Ethics and Law,” April 15, 2009.

A typology also anticipated by the research plan that currently frames the work of our CGREAL colleagues at Case Western Reserve University. Juengst E. , NIH Grant Application # 2 P50-HG003390–06, “Center for Genetic Research Ethics and Law,” April 15, 2009.

World Medical Association Declaration of Helsinki, “Ethical Principles for Medical Research Involving Human Subjects,” available at <http://www.wma.net/en/30publications/10policies/b3/> (last visited December 7, 2012); Levine R. J. , “The Need to Revise the Declaration of Helsinki,” New England Journal of Medicine 341, no. 7 (1999): 531–534.

Note how early-phase melanoma research is described and discussed in Harmon A. , “Target Cancer' Series,” New York Times, available at <http://topics.nytimes.com/top/news/health/series/target_cancer/index.html> (last visited December 7, 2012).

Bubela T. M. and Caulfield T. A. , “Do the Print Media ‘Hype’ Genetic Research? A Comparison of Newspaper Stories and Peer-Reviewed Research Papers,” Canadian Medical Association Journal 170, no. 9 (2004): 1399–1407; Caulfield T. , “Biotechnology and the Popular Press: Hype and the Selling of Science,” Trends in Biotechnology 22, no. 7 (2004): 337–339; Lau D. Ogbogu O. , and Taylor B. , “Stem Cell Clinics Online: The Direct-to-Consumer Portrayal of Stem Cell Medicine,” Cell Stem Cell 3, no. 6 (2008): 591–594.

Sutherland W. J. Bellingan L. , and Bellingham J. R. , “A Collaboratively-Derived Science-Policy Research Agenda,” PLoS One 7, no. 3 (2012): e31824.

Emanuel E. J. and Menikoff J. , “Reforming the Regulations Governing Research with Human Subjects,” New England Journal of Medicine 365, no. 12 (2011): 1145–1150.

Presidential Commission for the Study of Bioethical Issues, Moral Science: Protecting Participants in Human Subjects Research (December 15, 2011).