In response to President Barack Obama's Executive Order of 9 March 2009, the National Institutes of Health (NIH) has released the guidelines Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The guidelines were issued after publication in the Federal Register and a period of public comment that ended on 26 May. According to a press release from the NIH by acting director Raynard S. Kington, more than 49,000 comments were received and reviewed, and the guidelines issued on 7 July included responses to these comments.
The guidelines apply to NIH funds that can be used in research involving human embryonic stem cells (hESCs) and certain uses of induced pluripotent stem (iPS) cells. The guidelines also clearly state the ways in which NIH funding cannot be used—specifically, the introduction of hESCs or iPS cells into nonhuman primate blastocysts, research involving breeding of animals in which introduction of hESCs or iPS cells may contribute to the germ line, or derivation of stem cells from human embryos or research using hESCs created expressly for research purposes.
The aim of the guidelines is to clarify the manner in which hESCs that are derived in the future will be eligible for NIH funding, as well as to put into place a process by which hESCs that were derived prior to the effective date of the guidelines could be made eligible for NIH funding. For the purposes of the NIH, hESCs are defined as cells derived from the inner cell mass of blastocysts, capable of dividing without differentiation for a prolonged period in culture and known to develop into cells and tissues of the three primary germ layers. The NIH makes the point that, while hESCs are derived from embryos, they are not themselves considered human embryos. Research on hESCs is subject to the more general Department of Health and Human Services regulation contained in the Code of Federal Regulations, Title 45, Part 46, Subpart A (“Protection of Human Subjects”).
The specifics of the guidelines for the future development of hESCs that are eligible for funding (in Section II.A.) included the points that (i) the hESCs should be derived from human embryos created by in vitro fertilization for reproductive purposes and that are no longer needed for this purpose; (ii) the cells should be donated by individuals seeking reproductive treatment who gave voluntary written consent for the embryos to be used for research purposes, and policies must be in place to obtain such consent, making donors aware of all options available for use of these embryos; (iii) no payments may be offered; (iv) the donor is not to be coerced in any way; and (v) there should be a clear separation between the decision to create the embryo for reproductive treatment and the decision to donate the embryo for research purposes. With respect to the latter decision, the NIH guidelines suggest that the attending physician responsible for reproductive clinical care and the researcher seeking consent for research use of the embryos be different people.
Other points in the guidelines are that the consent for use of the embryos for research purposes should be obtained at the time of the donation—i.e., for this purpose, consent given at the time of generation of the embryo for reproductive therapy is not optimal—and that donors retain the right to withdraw consent until the time point at which the hESCs are generated or “permanently de-identified.” The consent form must clearly describe the procedure for generating hESCs (implying that the embryo will be destroyed in the process) and explain that the donor can expect no financial or direct medical gain from the derived hESCs. One key point is that the donor cannot restrict who may subsequently benefit from the use of the derived hESCs.
Section II.B of the guidelines provides a potential avenue by which hESCs derived from embryos donated before the effective date of the current guidance could be studied using NIH funds. This process will be guided by the recommendations of the Working Group of the Advisory Committee to the Director (ACD), which will review materials submitted by investigators that essentially document that the embryos used were obtained in a fashion consistent with the above principles. This will also apply to embryos donated outside the United States. The ACD, a committee chartered by the Federal Advisory Committee Act, will make recommendations to the Director of the NIH, who will make final decisions. Importantly, the working group will not undertake new evaluation of ethical standards but will consider submitted applications on the basis of the principles and points in the guidelines. Thus, this process will probably enable NIH-funded use of preexisting embryos or lines that were obtained in a rigorously consented fashion. The NIH will establish a new registry listing hESCs that are eligible for use in NIH-funded research.
It would seem that these guidelines have been carefully developed with input from a large swath of the scientific community. The previous policy (under former president George W. Bush) had allowed funding to support a limited number of hESC lines that existed prior to 2001. Many in the scientific and lay communities have suggested that this funding restriction has delayed scientific progress, and the issue became politicized, particularly during the lead-up to the last presidential election. Many institutions and states developed separate funding streams to allow work to be carried out on “non-NIH-approved lines,” surely a significant inefficiency. In the meantime, the development of iPS lines, which are not derived from human embryos, has diverted some focus away from hESCs. It will be interesting to see whether these new guidelines accelerate progress in the field at a demonstrable rate. It is likely that a long view will be needed to assess the development of any cellular therapy based on hESCs.