Posted on November 3, 2021 at 9:24 AM
by Kevin Wilger, MS
Earlier this year, the International Society for Stem Cell Research (ISSCR) released their updated Guidelines for Stem Cell Research and Clinical Translation to keep up with several advancements in the fields of genome editing, stem cell, and embryonic research. Most notably, the updated guidelines softened the “14-day rule,” which prohibited researchers from growing human embryos past 14 days after fertilization. The guidelines argue that, if broad public support and local regulations permit, some studies of embryos grown past 14 days could be justified. However, there are a number of gaps in ethical reasoning in the new guidelines that should give bioethicists, regulators, and legislatures pause before approving any protocols that exceed 14 days.
First, the new guidelines largely ignore the historical discussion around the first setting of the 14-day rule. One of the pivotal studies in embryo policy was the UK’s “Report of the committee of inquiry into human fertilisation and embryology,” commonly called the “Warnock Report,” published in 1984. The Warnock Report notes the following ethical considerations: 1) embryos having a special status as a member of the human species 2) circumstances that allow for the use of embryo research 3) the development of the CNS and the feeling of pain 4) when an embryo becomes an individual human. However, in recommendation 22.214.171.124 of the ISSCR guidelines (which softens the 14-day rule) these ethical considerations are not raised. The recommendation itself calls for a new policy discussion given the advances in technology and the benefits to human health and wellbeing. This largely echoes authors Insoo Hyun, Amy Wilkerson, and Josephine Johnston’s recommendation from 5 years ago when the development of embryos past 14 days first became technically feasible (which is unsurprising given that Hyun is a member of the steering committee for the ISSCR guidelines). In their article, Hyun et al. do in fact recognize the ethical reasons for setting 14 days, but argue that the cut-off was, “never intended to be a bright line denoting the onset of moral status in human embryos,” but a public policy tool that shows respect for differing views in human embryo research. While that is ultimately true in the case of the Warnock Report, it does raise the question of what circumstances have changed so that the respect for differing views should be rebalanced. Certainly, in some jurisdictions the debate on the status of the human embryo and its worth has not subsided.
The entire guideline section, “culture of human embryos beyond formation of the primitive streak or 14 days,” subtly suggests that researching past 14 days could be justified because it may prevent development disorders, improve fertility, and add to scientific knowledge. This leads to the second gap, it is unclear what role new embryo culture techniques and their eventual benefits would play in the removal of the 14-day rule (or the setting of any new rule). It is undisputed that invasive study of human organisms all along their development would yield tremendous clinical advantages. It will always be the case that expanding the window of embryo research to 15, 28, 72, etc. days will yield more scientific and clinical knowledge. This applies to all kinds of fields; even to my own field in treating human aortic aneurysms. Yet, no matter how worthy my research ends are for future generations, there are limitations to experimenting on humans and their aortas. The good intentions of the research are only one piece of the ethical puzzle. The ISSCR itself recognizes that at some point the research subject’s well-being is primary compared to future patients (see the Principle of the Primacy of Patient/Participant Welfare in the guidelines). Thus, the advances in technology and subsequent benefits seem to be irrelevant or less valuable in informing what embryo scientists should be allowed to do. Surely, the committees that recommended the 14-day rule previously (such as Warnock) also knew that more beneficial knowledge could be obtained by studying human development past 14-days, so why is it pertinent now?
Finally, there is a general sense around the publication of the new guideline that the pace of the science is making it difficult to set any new cut-off for the 14 day rule. For example, Jianping Fu, a biomedical engineer at the University of Michigan and a working group member of the ISSCR guidelines told Nature, “The science is progressing so fast, it was hard to draw another stop sign as a scientific community.” This is an unfortunate quote because it gives the impression that the progression of human embryo science comes prior to ethical deliberation for the ISSCR. To be fair, the recommendation still preserves legal approval and institutional review, but as a society the science speed prevents the ISSCR from setting any new prohibitions. As discussed above, the logical connection between the speed of science and the ethical cut-off for the prohibition of human experimentation is unclear. Should this not give bioethicists, regulators, and legislatures pause? It appears the people that are experts in human development cannot agree on when they should stop experimenting with human organisms.
Bioethicists, regulators, legislatures, and the public at large now have the responsibility to respond to this development from the ISSCR. It seems that if the rapidity of the science is one of the hindrances to deliberating and setting further prohibitions, then the prescription would be to slow down or halt any proposals of experimenting on embryos past 14 days. There must be a robust discussion on the status and the value of the 15-day old embryo and at what point in gestation experimentation must cease. If not, the technological advances that are meant to safeguard and promote human life, could end up endangering it.