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How to Determine Whether Existing Human Embryonic Stem Cell Lines Can Be Used Ethically

2008; Elsevier BV; Volume: 3; Issue: 3 Linguagem: Inglês

10.1016/j.stem.2008.08.012

1934-5909

Jeremy Sugarman, Andrew W. Siegel,

Biomedical Ethics and Regulation

Determining when it is ethically appropriate to use existing human embryonic stem cell (hESC) lines can be challenging for scientists as well as oversight bodies. Here, we identify such challenges and offer an approach to addressing them. Various guidelines have been issued regarding the ethical oversight of human embryonic stem cell research. For example, the National Academies of Sciences (NAS) issued guidelines in 2005, with amendments in 2007 (Committee on Guidelines for Embryonic Stem Cell Research, National Research Council, 2005Committee on Guidelines for Embryonic Stem Cell Research, National Research CouncilGuidelines for Human Embryonic Stem Cell Research. National Academies Press, Washington, DC2005Google Scholar, Human Embryonic Stem Cell Research Advisory Committee, National Research Council, 2007Human Embryonic Stem Cell Research Advisory Committee, National Research Council2007 Amendments to the National Academies' Guidelines for Human Embryonic Stem Cell Research. National Academies Press, Washington, DC2007Google Scholar). The International Society for Stem Cell Research (ISSCR) also released guidelines in 2006 (International Society for Stem Cell Research, 2006). Both sets of guidelines call for oversight of this research by ESCROs (Embryonic Stem Cell Research Oversight committees, under NAS) or SCROs (Stem Cell Research Oversight mechanisms, under ISSCR). The guidelines include a variety of provisions depending upon the type of research being proposed. While both sets of guidelines place considerable emphasis on provisions for deriving new hESC lines, they also suggest truncated review of research that involves the use of existing hESC lines. Much of the review process described in the guidelines focuses on the provenance of the hESC lines. The NAS indicates that the review process must involve “documentation of the provenance of the cell lines including: (i) documentation of the use of an acceptable informed consent process that was approved by an Institutional Review Board or foreign equivalent for their derivation . . . and (ii) documentation of compliance with any additional required review by an Institutional Animal Care and Use Committee (IACUC), Institutional Biosafety Committee (IBC), or other institutionally mandated review” (Human Embryonic Stem Cell Research Advisory Committee, National Research Council, 2007Human Embryonic Stem Cell Research Advisory Committee, National Research Council2007 Amendments to the National Academies' Guidelines for Human Embryonic Stem Cell Research. National Academies Press, Washington, DC2007Google Scholar). Under ISSCR's guidelines, the review process must “include a determination that the provenance of the human embryonic stem cell lines to be used has been scrutinized and deemed acceptable according to the principles outlined in this document, and that such research is in compliance with scientific, legal, and ethical norms” (International Society for Stem Cell Research, 2006). Despite what seems to be consensus regarding the need to assess provenance, neither of these guidelines explicitly defines the specific use of the term itself. A common dictionary definition of “provenance” denotes origin or source, or “the history of ownership of a valued object” (see Merriam-Webster Online). However, the guidelines intimate that the task is more comprehensive, involving information about gamete and embryo donors, the physical settings in which biological materials were obtained, and the presence and nature of any ethical or other institutional oversight involved. Further, the guidelines imply that oversight committees make ethical judgments concerning the information about provenance that is obtained. Nevertheless, little guidance is offered regarding how to make such assessments. This lack of specific direction can leave scientists uncertain about which cell lines might be appropriate to use in their research and puts oversight committees in a challenging position when they are asked to make such determinations on behalf of the researchers (e.g., Streiffer, 2008Streiffer R. Hastings Cent. Rep. 2008; 38: 40-47Crossref PubMed Google Scholar). We developed a stepwise approach to aid in determining whether a proposed use of a given hESC line is appropriate (Figure 1). The approach assumes that due diligence is exercised in obtaining the information necessary to conduct an assessment of provenance. When a specific use is proposed, it can easily be permitted if the evidence indicates that the hESC line was derived consistent with current standards. In contrast, if a preliminary review provides (1) evidence indicating a prima facie failure to satisfy current guidelines or (2) a lack of evidence that practices adhered to current guidelines, then deliberation is required. Deliberations involve consideration of the underlying ethical principles in context. Contextual features should help determine whether to make an exception to the current guidelines and permit the proposed use. Contextual features may include articulated policy statements or laws, information about the research environment, and information about the setting in which the embryos used in hESC research were created. Note that this approach does not necessarily rely solely upon published and available documentation of consent and review procedures. While such documents, if available, may facilitate the review process, a robust evidentiary base may arguably include other information. For instance, discussion with experts in the field may provide evidence of acceptable standards in place at the time, or of local review processes that were utilized. A central question to address during deliberation is whether the ethical principles underlying provisions of extant and current guidelines are violated by permitting use. An example should help make this clear. An investigator approached our ESCRO about using hESC lines from Stemride International. We obtained published information about the lines in question, as well as a copy of the informed consent document that was used with embryo donors, and minutes from the institutional review board that reviewed the proposed research. We also consulted with the investigator who derived the lines to resolve some questions not answerable with these materials. Careful examination of the information acquired yielded no evidence that the consent process informed embryo donors that their embryos would be destroyed in the course of creating the hESC lines, which is a required provision in current guidelines for hESC research. In other words, there was prima facie evidence that the standards for hESC research were not adhered to, resulting in the need for deliberation that would take into account the relevant contextual features. One important contextual feature is the articulated ethics guidance that existed at the time the lines were derived. If such guidance was indeed satisfied, then even if current guidelines are more stringent, and thus not satisfied, it may yet be permissible to use the lines. That is, provided that investigators acted substantially in accord with underlying ethical principles (e.g, respect for autonomy), adherence to the less stringent guidelines may be considered sufficient. In this particular case, however, the extant guidance documents clearly required that donors understood that the embryos would be destroyed in the process of deriving hESC lines. This point provided further support for the prima facie claim disallowing the use of the Stemride hESC lines. Nevertheless, we next considered the setting in which the embryos were generated. In this example, the embryo donors were recruited from a clinic that was utilizing preimplantation genetic diagnosis; the hESC lines were derived using either “diseased” or “healthy” embryos. Arguably, donors who were involved in using preimplantation genetic diagnosis to select embryos would not be expected to be morally opposed to destruction of those embryos with genetic abnormalities; however, it is unclear whether the donors would feel similarly about those embryos that could potentially be used for in vitro fertilization. Based on these contextual features, our ESCRO decided that the investigator could use the diseased hESC lines consistent with the ethical principles underlying the standards for hESC research, but not the healthy lines. The systematic approach to assessing provenance information about hESC lines we describe here should be helpful to SCROs and ESCROs in making determinations concerning the ethical use of particular cell lines. An advantage of this approach is that it makes the processes of practical and moral reasoning more explicit. As additional experience is garnered the approach may need to be modified and adjusted. International Society for Stem Cell Research. (2006). Guidelines for the conduct of human embryonic stem cell research. http://www.isscr.org/guidelines/index.htm.Merriam-Webster Online. (2008). “Provenance.” http://www.merriam-webster.com/dictionary/provenance.Stemride International. (2008). List of hESC lines. http://www.stemride.com/products_lines.htm.