On July 6, the Obama administration released its much anticipated final guidelines on human stem cell research. They represent a significant advance over Bush’s policy in terms of both science and ethics, but the administration also missed an important opportunity to “normalize” human embryonic stem cell (hESC) research, which would have made the guidelines even better and could have permanently altered the terms of the public debate.
The most significant difference between Obama’s policy and Bush’s policy is the expansion of which hESC lines are eligible for federal funding. Both policies require that the stem cell line be derived from an embryo that meets three criteria: it was originally created using in vitro fertilization for reproductive purposes but was no longer needed for those purposes, it was donated with voluntary and informed consent, and it was donated without payment. But in an attempt to avoid tax-payer complicity in the future destruction of embryos for hESC research, Bush added a fourth criterion: the line had to have been derived prior to the date he articulated his policy, August 9, 2001.
Although Bush claimed that there were 64 eligible lines, a mere 21 were available for distribution. Obama’s final guidelines, in contrast, are expected to allow funding for research using most of the estimated 700 hESC lines already in existence. These lines will be evaluated by an Advisory Committee to the Director of the NIH charged with reviewing their provenance for compliance with the core ethical principles of voluntary, informed consent and other long-standing principles of human subjects research. Lines derived in the future will also be eligible for funding, in contrast to Bush’s policy, as long as they meet the guidelines’ detailed requirements for informed consent, acceptable procedural safeguards, and appropriate documentation.
Neither policy allows federal funds to be used for the process of deriving new hESC lines, as the only established derivation method requires destroying a human embryo, the funding of which is prohibited by the Dickey-Wicker Amendment.
As the NIH reviews applications, it will compile a registry of all hESC lines eligible for federal funding, thus avoiding duplication of the laborious search for provenance documentation and relieving local oversight committees of its review.
As expected, researchers are tremendously excited about the scientific advantages of funding for the expanded diversity of lines, especially lines carrying specific genetic diseases, lines derived under carefully defined media conditions free of any animal products, and lines derived using refined protocols that make freezing and thawing more efficient. It is worth noting, though, that Obama’s policy has ethical advantages over Bush’s policy as well.
Under Bush’s policy the NIH played no role in setting standards for the procurement of embryos for deriving new hESC lines. No matter how an embryo was procured for hESC research, all resulting hESC lines would be ineligible for federal funding. Under Obama’s policy, when an applicant proposes to use an hESC line in federally funded research, the NIH will review the procurement process for the embryo from which that line was derived, applying standards that attempt to capture our best current understanding of how to do this ethically. With expanded funding comes expanded oversight, and with expanded oversight comes the ability to set and enforce ethical standards.
The ethical standards in the new guidelines are not perfect. One significant shortcoming is that they do not require, as the National Academy of Sciences’ 2005 voluntary guidelines do, that embryo donors be informed that their cells might be used to make human/nonhuman chimeras. Social science research continues to document significant public opposition to many kinds of animal/human mixing, and failing to inform embryo donors about this research raises the troubling possibility that their cells could be used in ways they find morally objectionable.
Some public comments urged the NIH to grandfather all hESC lines in existence before the effective date of the guidelines, regardless of whether they came from embryos donated with ethically valid consent. The NIH rejected this request, noting that “the principles of ethical research, e.g., voluntary informed consent to participation, have not varied in this time period.”
This willingness to take informed consent seriously also represents a significant ethical advantage over the Bush administration’s approach. Although Bush’s policy officially restricted eligibility to lines derived with informed consent from the embryo donors, local ESCRO committees, charged by the National Academy of Sciences’ 2005 guidelines with reviewing the provenance of hESC lines, were unable to obtain documentation of informed consent from the NIH.
Finally, as I wrote last year in the Hastings Center Report, a Freedom of Information Act request made the consent forms used by the embryo donors publicly available, revealing that some lines on Bush’s registry had not been derived with informed consent, that others had been on the registry years before the donors had given permission for their cells to be redistributed, and that some donors were not adequately informed about the research that was going to be done with their cells.
NIH insiders anonymously reported that the Bush administration, in an attempt to placate the scientific community’s vocal concerns about the small number of lines eligible for federal funding, had wanted as many lines as possible on the registry, with one insider quoted as saying “We essentially had a gun held to our heads.” Although NIH officials publicly responded to the consent problems by saying that the “NIH staff were careful to consider the president's criteria set forth in 2001, including the requirement for informed consent,” another Freedom of Information Act request for any and all documentation regarding the NIH’s deliberations on this issue turned up no “responsive documents.”
Despite acknowledgement of the consent problems by ESCRO committees at prominent research universities, the California Institute for Regenerative Medicine, and the United Kingdom’s Stem Cell Bank, the Bush administration refused to de-list the problematic lines or even to acknowledge that there were any issues. This was especially problematic because several other oversight bodies that had publicly committed themselves to only allowing hESC research using lines derived with informed consent from the embryo donors had already allowed the use of the lines on Bush’s registry, mistakenly assuming that the NIH had satisfactorily reviewed their provenance.
The Bush administration’s lack of transparency and integrity thus put the practices of the NIH and these other institutions in direct conflict with the ethical standards to which they had publicly committed themselves. This is a recipe for undermining the public’s trust in the hESC research community. Obama now has the opportunity to remedy these ethical failures and to ensure that similar mistakes are avoided in the future.
Obama’s guidelines would have been better still had the NIH not rejected a proposal made in the public comments to end human embryonic stem cell exceptionalism, the idea that hESC research is so ethically problematic that it merits its own distinctive set of institutions, rules, procedures, and standards.
Rather than trying to draft a new, parallel system of oversight for hESC research, the NIH could have simply folded the oversight of hESC research into the existing federal regulations for the protection of human research subjects, known as the Common Rule, with one important change.
The Common Rule allows institutional review boards (IRBs) to waive informed consent for research using already-existing samples that cannot be linked to their donors. Thus, IRBs routinely allow surgical waste and leftover pathology samples to be anonymized and handed over to researchers without the patient’s informed consent. Few people, however, view their embryos as morally analogous to leftover clinical specimens and there is a robust consensus that informed consent should not be waived in the context of hESC research.
Using the Common Rule sans waivers to effect hESC research oversight has much to recommend it. It would alleviate the pressure to provide separate review of hESC research by ESCRO committees, a time-consuming process that arguably adds little value above the reviews performed by IRBs and animal care and use committees.
In one public comment, Bernard Lo, Alta Charo, Jonathan Moreno, George Daley, and Richard Hynes compared each aspect of the draft guidelines with its analogue in the Common Rule, and they made a compelling argument that such a system would not only “relieve barriers to responsible hESC research,” but would also “represent a level of rigor, transparency, and accountability that the draft guidelines do not offer.” Full IRB oversight without waivers would have been better, both in terms of efficiency and in terms of ethics, than Obama’s policy.
And if the NIH had taken this opportunity to normalize hESC research, there is the distinct possibility that this would have significantly altered the tone of the public debate. It would have sent a clear message to the public that this research is just as praiseworthy and important, and just as ethical, as the many other kinds of human subjects research that scientists perform every day to advance our understanding of the world and of ourselves.
Robert Streiffer, Ph.D., is associate professor of philosophy and bioethics at the University of Wisconsin, Madison. His investigation of informed consent obtained for stem cells eligible under the Bush policy received widespread press coverage, prompted institutions to reconsider their use of some stem cell lines, and alerted the Obama administration to the need for greater sensitivity to consent issues when it drafted the new guidelines for stem cell research.