Ethical, legal, and social considerations in conducting the Human Microbiome Project.

The early days of the genomic revolution—from the Asilomar Conference on Recombinant DNA in 1975 to the founding of the Human Genome Project in 1990—were marked by awareness among researchers, government officials, and policy makers that emerging scientific knowledge raised a host of ethical, legal, and social challenges. Scientists now undertaking research on the human microbiome—including those engaged in the National Institutes of Health’s (NIH) latest Roadmap initiative, the Human Microbiome Project (HMP)—confront a similarly uncharted ethical landscape. Not only does the conduct of human microbiome research raise important ethical considerations, but the long-term implications of the HMP also present the possibility of fundamental shifts in understandings of human life and health. The HMP is one of several international efforts to use metagenomic analysis to study human health. It is estimated that there are 10 times as many microbial cells than human cells in and on our bodies (Turnbaugh et al. 2007). We already know that human microbiota (i.e., all the microorganisms that inhabit the skin and mucous membranes) in certain sites of the body play an essential role in maintaining health and normal function (e.g., synthesis of vitamin K in the intestinal tract) (Lupp and Finlay 2005). The HMP aims to create a reference catalogue of microbial DNA that can be used as a resource to explore whether or not humans have a “core” microbiome (i.e., a microbiome that is common to all humans); whether there is stability in an individual’s microbiota through different periods in that individual’s life; whether there are similarities in microbiomes within families, communities, and different environments (Palmer et al. 2007); and ultimately, whether or not changes in the human microbiome can be correlated with changes in human health. A total of $8.2 million was awarded in 2007 to four institutions (Baylor College of Medicine, The Broad Institute, The J. Craig Venter Institute, and Washington University) to conduct the first phase of human sampling in the HMP. Samples are being collected from ∼250 healthy adults from five body sites: the oral cavity, skin, nasal cavity, gastrointestinal tract, and vagina, for a total of 18 subsites for women and 15 subsites for men. Peripheral blood is also being collected for human DNA sequencing and serum banking (to evaluate possible immune responses to the microbiome). Subjects will be screened using a general health questionnaire. Exclusion criteria for conditions that may influence the stability of the microbial environment, including taking specific medications (e.g., antibiotics, immunosuppressive agents), major dietary changes, history of cancer (exception of certain skin cancers) or chronic immune-mediated disorders (e.g., inflammatory bowel disease, psoriasis), history of chronic candidiasis (yeast infection), or active sexually transmitted diseases (e.g., gonorrhea) within the previous 2 mo for females. Children under the age of 18 and adults beyond the age of 40 will be excluded because of the need for a relatively uniform human population, especially considering the sample size and extent of potential variation within the human microbiome. Concerns about profound physiologic changes during adolescence and menopause in women also necessitate tighter boundaries to the age range. Each subject will provide at least one set of specimens within the first year, and at least 50% of these individuals are expected to participate in follow-up sampling within 12 mo of the initial sampling at all body sites. At least 10 subjects will be invited back for more extensive and invasive sampling at all body sites. All microbial DNA sequence data will be coded and released into publicly accessible databases. Clinical information that is collected will be coded and stored in a controlled-access database so that it can be correlated with analyzed data. Human DNA will be coded and stored for future analysis. Individual human DNA data will be released into controlled-access databases; aggregate data will be released into public databases. As the first phase of the HMP gets underway, it is important that the ethical, legal, and social implications of this research are carefully studied and responsibly managed. It is also essential that the research itself is conducted according to the highest ethical standards. Drawing on the significant body of scholarship that has amassed over the past two decades, and based on the involvement of two of the authors (A.L.M. and J.V.) with the first phase of the HMP, we identify five major ethical issues associated with conducting the HMP. This list is not exhaustive, and many of these issues are implicated in other areas of genetic research, but the complexity and exploratory nature of the HMP may, in some instances, necessitate modified resolutions.