By Kevin E. Noonan —
Yesterday, the National Institutes of Health released guidelines governing requirements (and limitations) for federal funding of research on human embryonic stem cells. These rules supersede rules promulgated during the Bush administration that so severely constrained the number of funding-eligible human stem cell lines as to effectively prohibit use of federal funds for this research. These Guidelines were promulgated by Acting Director Raynard S. Kington, and become effective today, July 7, 2009. The new Guidelines are expected to make up to 700 existing human embryonic stem cell lines eligible for federal funding, a ten-fold increase over the 69 hESC lines approved under the Bush administration (many of which have been acknowledged to be inappropriate for embryonic stem cell research).
The Guidelines were developed by the Institutes in response to Executive Order 13505, entitled "Removing Barriers to Responsible Scientific Research Involving Human Stem Cells" issued March 9, 2009. Fulfilling a promise President Obama made during his campaign, the Order was intended to permit the Institutes to "support and conduct responsible, scientifically worthy human stem cell research, including human embryonic stem cell (hESC) research, to the extent permitted by law." The new Guidelines, relating to both intramural and extramural research, "establish policy and procedures under which the NIH will fund such research, and helps ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law."
The Guidelines are expressly based on the principles that:
2. Individuals donating embryos for research purposes should do so freely, with voluntary and informed consent.
Human embryonic stem cells are defined as "cells that are derived from the inner cell mass of blastocyst stage human embryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers," making the distinction that "[a]lthough hESCs are derived from embryos, such stem cells are not themselves human embryos." The Guidelines establish a new NIH stem cell registry, and stem cells will be eligible for funding if they are listed on the registry or if they comply with Section IIA of the Guidelines. Cells will be eligible if they are derived from human embryos:
1. that were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose;
2. that were donated by individuals who sought reproductive treatment (hereafter referred to as "donor(s)") and who gave voluntary written consent for the human embryos to be used for research purposes; and
3. for which all of the following can be assured and documentation provided, such as consent forms, written policies, or other documentation, provided:
a. All options available in the health care facility where treatment was sought pertaining to the embryos no longer needed for reproductive purposes were explained to the individual(s) who sought reproductive treatment.
b. No payments, cash or in kind, were offered for the donated embryos.
c. Policies and/or procedures were in place at the health care facility where the embryos were donated that neither consenting nor refusing to donate embryos for research would affect the quality of care provided to potential donor(s).
d. There was a clear separation between the prospective donor(s)'s decision to create human embryos for reproductive purposes and the prospective donor(s)'s decision to donate human embryos for research purposes. Specifically:
i. Decisions related to the creation of human embryos for reproductive purposes should have been made free from the influence of researchers proposing to derive or utilize hESCs in research. The attending physician responsible for reproductive clinical care and the researcher deriving and/or proposing to utilize hESCs should not have been the same person unless separation was not practicable.
ii. At the time of donation, consent for that donation should have been obtained from the individual(s) who had sought reproductive treatment. That is, even if potential donor(s) had given prior indication of their intent to donate to research any embryos that remained after reproductive treatment, consent for the donation for research purposes should have been given at the time of the donation.
iii. Donor(s) should have been informed that they retained the right to withdraw consent for the donation of the embryo until the embryos were actually used to derive embryonic stem cells or until information which could link the identity of the donor(s) with the embryo was no longer retained, if applicable.
e. During the consent process, the donor(s) were informed of the following:
i. that the embryos would be used to derive hESCs for research;
ii. what would happen to the embryos in the derivation of hESCs for research;
iii. that hESCs derived from the embryos might be kept for many years;
iv. that the donation was made without any restriction or direction regarding the individual(s) who may receive medical benefit from the use of the hESCs, such as who may be the recipients of cell transplants;
v. that the research was not intended to provide direct medical benefit to the donor(s);
vi. that the results of research using the hESCs may have commercial potential, and that the donor(s) would not receive financial or any other benefits from any such commercial development;
vii. whether information that could identify the donor(s) would be available to researchers.
Alternatively (Section IIB), for stem cell lines established prior to promulgation of these Guidelines, eligibility can be established by submitting evidence to a newly-constituted Working Group of the Advisory Committee to the Director showing that "the hESCs were derived from human embryos: 1) that were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose; and 2) that were donated by donor(s) who gave voluntary written consent for the human embryos to
be used for research purposes."
The Guidelines expressly prohibit funding of research on human embryonic stem cells or pluripotent cells introduced into a non-human primate blastocyst or animal breeding experiments involving introduction of human stem cells into non-human primate blastocysts.
The Notice reports that the Institutes received around 49,000 comments in response to the request for public comment published on April 23, 2009 in the Federal Register (74 Fed. Reg. 18578). These comments came from "patient advocacy groups, scientists and scientific societies, academic institutions, medical organizations, religious organizations, and private citizens," as well as members of Congress. The Notice contains a synopsis of these comments, which are included in groups identified as title, terminology and background, financial gain, IRB review, donation and informed consent, and monitoring and enforcement actions, among others. The Notice describes how the draft guidelines were adapted or modified in response to these comments, or the Institutes distinguished or disputed the assertions in the comments. Of note is the Institutes' assertions that it expects "that stem cell research materials developed with NIH funds, as well as associated intellectual property and data, will be distributed in accordance with the NIH's existing policies and guidance, including ''Sharing Biomedical Research Resources, Principles and Guidelines for Recipients of NIH Grants and Contracts' and 'Best Practices for the Licensing of Genomic Inventions'" (see NIH Policies & Reports page). In addition, the Institutes will review de novo the circumstances surrounding development of existing stem cell lines rather than grandfathering these cells, applying ethical principles embodied inter alia in the Guidelines and 45 C.F.R. Part 46 Subpart A (Protection of Human Subjects).
The comments section also addresses the potential limitations on federal funding imposed by the Dickey amendment, wherein "an embryo is defined by Section 509, Omnibus Appropriations Act, 2009, Pub. L. 111-8, 3/11/09 . . . as any organism not protected as a human subject under 45 C.F.R. Part 46 that is derived by fertilization, parthenogenesis, cloning or any other means from one or more human gametes or human diploid cells." The Guidelines state that:
[s]ince 1999, the Department of Health and Human Services (HHS) has consistently interpreted this provision as not applicable to research using hESCs, because hESCs are not embryos as defined by Section 509. This long-standing interpretation has been left unchanged by Congress, which has annually reenacted the Dickey Amendment with full knowledge that HHS has been funding hESC research since 2001. These guidelines therefore recognize the distinction, accepted by Congress, between the derivation of stem cells from an embryo that results in the embryo's destruction, for which federal funding is prohibited, and research involving hESCs that does not involve an embryo nor result in an embryo's destruction, for which federal funding is permitted.
While nicely expressing the distinction, it remains to be seen whether Congress acts to refine the Institutes' understanding of these restrictions, in light of the expansion in the scope of human embryonic stem cells intended by these Guidelines to become eligible for federal funding.
July 6, 2009 – 
Patent Docs 