Recent research suggests that it may be possible to derive gametes from a variety of pluripotent stem cell (PSC) sources ([Clark et al., 2004],  [Geijsen et al., 2004],[Hubner et al., 2003],  [Nayernia et al., 2006b],  [Park et al., 2009]  and  [Toyooka et al., 2003]). Though preliminary, these findings may open doors to important discoveries in both basic and applied research. Furthermore, the science has already become a matter of debate and policy in at least two countries (Japan, 2000; United Kingdom, 2008a, 2008b). Significant hurdles face this science, as discussed below.

 

However, assuming that these obstacles can be overcome, the ability to create PSC-derived gametes raises a number of challenging ethical and policy issues that must be considered. To address such issues before they become pressing problems, we convened a group of more than 40 scientists, ethicists, journal editors, and lawyers to review and debate the challenges raised by PSC-derived gamete research. The objectives of this Hinxton Group (Hinxton Group, 2006) project included: (1) creating a road map for policymakers and the public, (2) providing relevant contextual information for applications related to PSC-derived gametes, and (3) providing guidance regarding ethical oversight. Here, we discuss the process and outcomes of the group's deliberations and our expansions on these deliberations in three parts: the state of the science, the societal implications, and recommendations.State of the Science

 

 

Though several scientists present at the meeting are directly involved in PSC-derived gamete research and therefore are likely to find it promising, others have no direct stake. Following considerable discussion, the group reached consensus that PSC-derived gamete research has “considerable scientific value and potential both for understanding basic mechanisms of gamete biology and overcoming clinical problems.” Thus far, scientists have been able to complete in vitro both the very early steps of gamete development from PSCs (e.g.,  [Clark et al., 2004],  [Geijsen et al., 2004],  [Hubner et al., 2003],  [Nayernia et al., 2006a],  [Novak et al., 2006],[Park et al., 2009]  and  [Toyooka et al., 2003]) and later maturation steps of gametes that originated in vivo (e.g.,  Picton et al., 2008), but the intermediary steps bridging these two stages are proving more difficult (e.g.,  Novak et al., 2006). The latter is not surprising, as relatively little is known of germ cell biology during this period, such as erasure of genomic imprinting and cell-cycle control for entry into mitotic arrest or meiosis. Indeed, although one group has reported obtaining live born mice from PSC-derived male gametes, these pups died shortly after birth from defects likely to be related to imprinting problems (Nayernia et al., 2006b). Getting all the way from a human PSC to a gamete capable of fertilization—entirely in vitro—is likely to be years away. At the same time, the science is paying dividends right now in addressing questions about the role of specific genes in early germ cell development and the interaction between germ cells and supporting somatic cells.