The trusted source for
healthcare information and
By J. Benjamin Hurlbut, PhD, assistant professor of Biology and Society in the School of Life Sciences at Arizona State University, Tempe
Editor’s note: Considering the far-ranging implications of gene editing of germline cells outlined at a recent international summit, IRBs may be at somewhat of a loss as to their current and future role in this emerging body of research. We sought out someone who ponders these imponderables for a living, and here follows his assessment of possible roles IRBs may play as this line of research unfolds.
It strikes me that IRBs can and should play a role in the emerging public discussion about germline applications of gene editing, even if only by making quite clear how they are limited in their jurisdiction and remit to evaluate research in this area. The range of research that is at issue is quite broad. There is certainly the potential for experiments that would fall within IRB jurisdiction by virtue of involving human subjects — that is, experiments that involve transferring “edited” embryos or embryos created with edited gametes. But to my knowledge no one is contemplating this or advocating it at this time.
A few ways that IRB jurisdiction may kick in could include the following:
Yet researchers’ responsibilities to seek consent from donors are limited in all the standard ways (e.g., if consent has already been given at the time of donation, including if generically for “research” or if the tissues are anonymized). Thus, there is nothing special about the research per se that might place it within the jurisdiction of IRBs.
This is odd, given the fact that the most affected human subject from “clinical applications” of this technology is a person who does not yet exist, and thus isn’t really given consideration as such. It is worth reflection upon the fact that no matter how thorough the risk assessments, there can be no circumstance under which this technology would be without risk for the child produced through it. A child who already exists and is being treated for a disease with a risky therapy is a radically different case than applying a technology to bring a child into existence who may be affected in unknown ways. This is, I think, something IRBs ought to be reflecting upon.
Indeed, there have been a number of developments in assisted reproductive technology, including in vitro fertilization (IVF) itself, where the babies produced were de facto subjects of experiments, but were not accorded the protections normally accorded to experimental subjects, since when the experiments were initiated they did not (yet) exist: consider intra-cytoplasmic sperm injection (ICSI), cryopreservation, pre-implantation genetic diagnosis (PGD), and in vitro fertilization itself. Indeed, the ways IRBs are tasked with thinking about and protecting human subjects does not fit well with the kinds of risks that these technologies may pose to human beings who do not yet exist — and who will not exist but for the very application of the questionable technology.
This points to something important: a lack of clarity over what institutional oversight body or mechanism has authority— or ought to have authority — over such research. Some institutions have Embryonic Stem Cell Research Oversight committees (ESCROs), which are mostly voluntary, though required by law in a few states. There is variation between them in terms of what kinds of research they have jurisdiction over. Would gene editing research on human embryos require ESCRO review at an institution that has an ESCRO? Perhaps, but not necessarily. What about institutions that don’t have such bodies? A human embryo in vitro is not considered a human subject under federal regulations, and though there are many Americans who think embryos are persons and should be treated as such, there are many others who do not. It is not necessary, though, to answer that particular question to recognize that there are ethically difficult issues — or, if you prefer, issues about which there are deeply held beliefs and conflicting opinions. So, it does seems reasonable that a research institution ought to have well-established and transparent processes for reviewing and deliberating over the appropriateness of particular proposals for research in this domain.
I think these questions apply (or ought to apply) not just to research on “human subjects” but to research that is not intended to be “clinical,” but aspires to move technique in that direction. After all, this is a very sensitive domain, and if clinical applications are in principle unimaginable for the reasons outlined above, then drawing a bright line between such applications and mere research, and saying nothing goes for the former and anything goes for the latter seems problematic. It is problematic because it imposes a rather artificial distinction between a range of activities that are linked — and are intended to be linked.
In my view, the most important question to ask about institutional structures like IRBs is whether they are adequate to the task of engaging in the forms of thoughtful reflection and deliberation that techniques like application of gene editing to human gametes and embryos warrant. There has been a general affirmation that a public dialogue is needed. Yet the most sustained dialogues are likely to happen in institutional spaces whose charge it is to engage in them, not bodies that have secondarily elected to take up the issues. The remit of IRBs does include these sorts of issues.
IRBs might reflect, therefore, on their own jurisdictional remit, and the ways in which they are invited to contribute, or precluded from contributing, to the work of shaping applications of these techniques in research. IRBs are spaces where questions can be asked that might otherwise not be — for instance, questions on how to think about ethical obligations to the human subject who will also the experimental product of these techniques. Yet the range and focus of questions is potentially constrained, and may as a result leave aside questions that if asked earlier on, would orient trajectories of research — and of corollary ethical discussions — in better directions. It is particularly important for IRBs to think about how they stand in relation to other oversight bodies that would potentially deal with such research, and whether, taken together, those bodies are capable of addressing the issues that IRB members or others see as significant. By making explicit their sense of their own jurisdictional remit, and inviting other oversight bodies to do the same, they would make more visible the questions that may go unasked and the cracks through which key issues might fall.
For an area of research like this, my sense is that there are a lot of questions that go unasked, and that this is in no small part because of prior commitments to ideas of what matters to ethical oversight bodies, and what is beyond their focus or remit. One of the points I tried to make in a recent article1 was that we confront these questions suddenly and urgently not because we couldn’t have anticipated them, but because we have excluded the capacity to anticipate them from institutionalized mechanisms of oversight, reflection and deliberation, often because they have been deemed too hypothetical, to complex, or someone else’s responsibility. Engendering the capacity to develop awareness of what questions go systematically unasked, and in what ways the workings of bodies like IRBs contribute to this, is an important thing for such bodies to do, not least because people tend to think that because structures like IRBs exist, problems are being taken care of. IRBs should be more reflexive and explicit about what they are not taking care of. They can do this more effectively if they imagine possible experiments and reflect on what dimensions of them are outside of their purview, but maybe ought not be.
It is indeed possible that even IRBs that do not do what I have suggested above may eventually have a protocol land on their agenda that involves human germ-line gene editing. The complex ethical questions associated with such research cannot be solved purely by technical assessment of risk and safety, although there will be pressure to limit deliberation to such issues. The problem is not merely a matter of having adequate knowledge, but of having developed the capacity to think well about these challenging possibilities. If that means recognizing the limits of IRBs’ capacity and authority to review such research, then that should be recognized up front as a problem, and not taken as an indication that there is nothing here that warrants reflection and review. One of the central problems of governing research in this domain is determining how — and by whom — such problems will be recognized and acted upon.
Financial Disclosure: Editor Melinda Young, Senior Staff Writer Gary Evans, Managing Editor Jill Drachenberg, Associate Managing Editor Dana Spector, Physician Reviewer Lindsay McNair, MD, MPH, MSBioethics, and Nurse Planner Kay Ball, RN, PhD, report no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.