May 22, 2009
Re: “National Institutes of Health Guidelines for Human Stem Cell Research”
We welcome and applaud the leadership that the NIH proposes to assume for the oversight of human embryonic stem cell research in the United States. The draft guidelines represent an important step towards accelerating critical medical research by giving scientists access to more embryonic stem cell lines that better reflect the diversity in our society, make it possible to model inherited human diseases, and have favorable properties such as reduced contamination with animal products. Given the importance of human embryonic stem cell research to future medical progress, access to an increased range of lines will accelerate efforts to understand and treat major public health problems.
The International Society for Stem Cell Research (ISSCR) has already endorsed research on pluripotent stem cell lines derived via in vitro fertilization (IVF), somatic cell nuclear transfer (SCNT), parthenogenesis, or gene-based reprogramming. The ISSCR supports such stem cell research globally, where performed under rigorous standards of research ethics described in the 2006 ISSCR Guidelines for the Conduct of Human Embryonic Stem Cell Research. We reaffirm this position and encourage NIH to review its Guidelines for human embryonic stem cell research as the science in this area evolves. In the interest of improving world health we urge the NIH to open discussions on funding research carried out with human pluripotent stem cell lines derived from sources other than excess reproductive IVF embryos, including SCNT embryos, if they become available and are derived under rigorous ethical standards.
The NIH draft guidelines represent an important advance beyond the Bush administration policy, but could be significantly improved by addressing two key issues. If these issues are not addressed, the guidelines may have the unintended effect of delaying and hampering ethical stem cell research.
1) The new informed consent standards set forth in the draft NIH policy would establish comprehensive scientific and ethical standards for the derivation of lines in the future, after the institution of this policy. However, retroactive application of these standards to existing lines will exclude from federal funding many, perhaps most, lines that have been in routine use for the past ten years, and about which substantial and essential information is already available. It is critical that a mechanism be developed to ensure that the past ten years of scientific progress with these lines not be lost to federally-funded research, and to ensure that researchers do not have to start from scratch to characterize new lines for studies that began with the older lines. If the NIH does not reconsider how existing human embryonic stem cell lines can be evaluated for eligibility for federal funding, we will find ourselves in the untenable position of excluding many lines that were derived under terms that were judged appropriate in the past by institutional oversight boards.
To remedy these potential problems, the ISSCR recommends that instead of providing specific criteria using very detailed language for informed consent, the NIH define a deliberative review process to establish eligibility for federal funding of human embryonic stem cell lines derived prior to July 2009. These pre-existing lines would be considered ethically derived and eligible for federal funding if they were derived according to each of the following core principles:
A. Voluntary informed consent: That those persons who donated embryos or other human materials for the derivation of human embryonic stem cell lines were empowered to make a voluntary and informed decision to participate or to refuse to participate in the research;
B. No undue inducement: That the voluntary nature of the informed consent process was not undermined by undue inducements or other undue influences to participate in the research; and
C. Independent review and oversight: That the derivation process and informed consent documents were reviewed and approved by an independent oversight committee such as an Institutional Review Board (IRB; or the equivalent in other countries).
The ISSCR believes a deliberative review process upholding these three core principles would be much more desirable and practical for all human embryonic stem cell lines, rather than relying on a set of specifically-worded eligibility requirements, as currently articulated in the draft NIH guidelines document. Such a vetting process would allow the grandfathering of existing stem cell lines that were derived according to the ethical standards prevailing at the time and place of derivation. This would also confer greater flexibility in the implementation of the constantly evolving standards for best practices in donor consent and international nuances of language. Under the review process, the use of existing lines could be evaluated on the basis of the regulations and ethical expectations at the time and place of embryo donation, so long as there is evidence that each of the three core principles was upheld. By stipulating a review process founded on core principles rather than specific language in informed consent documents, the NIH would provide oversight of stem cell research according to current standards of the Common Rule and existing IRB mechanisms for tissue research oversight.
2) We urge the NIH to itself develop a list of human embryonic stem cell lines that are eligible for federal funding. Having the NIH maintain such a list would avoid the potential problem of different organizations and institutions in different regions of the U.S. arriving at differing opinions about the eligibility of cell lines for federal funding. Clearly, such a list would have to be curated and updated regularly, and the NIH would need to develop a process whereby newly-derived cell lines could be considered for eligibility for federal funding. While such a centralized process might engender opposition by some, we note that such a system was previously used in the form of the RAC for certification of safety and eligibility of new vectors for recombinant DNA research. This system clearly worked in the past and was critical to the regularization of this important research.
The ISSCR welcomes further discussion during the deliberations of the NIH and offers their assistance at all stages of the process.
As you know, the ISSCR has exerted enormous effort to provide professional standards for the ethical derivation and use of human embryonic stem cell lines. In 2006, the ISSCR released its Guidelines for the Conduct of Human Embryonic Stem Cell Research, which seeks to ensure that human stem cell research is carried out according to rigorous standards of research ethics and to encourage uniform practices globally. The ISSCR built into these international guidelines high standards of informed consent to facilitate the translation of these standards into practice moving forward, and provided template documents for the donation of materials for human embryonic stem cell line derivation. We remain enthusiastic to work with the NIH to ensure that this research is appropriately regulated and able to fulfill its remarkable promise for enhancing human health.
Fiona M. Watt, DPhil
Irving L. Weissman, MD
*** The International Society for Stem Cell Research (ISSCR)
is an independent, nonprofit membership organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application.
Posted September 24, 2009