The 14-day rule is a well-known governing ethical policy whereby scientists are limited to research on human embryos to a maximum of 14 days post in vitro fertilization. Yet, many groups are suggesting extending the 14-day rule on the basis of technical feasibility and prospective benefits of researching unknown developmental events, postulated to significantly contribute to medical knowledge and the future of health care. Should the 14-day rule be extended and if it were, what would constitute the newly defined limits on embryo research?
By: Jenna Baffa
Jenna Baffa, having received an Honors BSc in 2020 in Biomedical Science, is now a 2022 MHSc in Laboratory Medicine candidate at the University of Toronto, specializing in the field of Clinical Embryology.
Before this program, Jenna had never taken an ethics course. In her 2nd semester, she was able to explore the field of ethics within pathology and embryology, sparking her interest to write this paper. She believes with an ever-expanding range of technology in the embryology world, there are questions that need to be asked on how we should define our limits. There is so much we are technically able to do, but the ethical questions lie in asking ourselves if it is permissible to do so. This paper was inspired by that notion, where she explore the ethical limits of the 14-day rule in embryo research.
The 14-day rule is a well-known governing ethical policy whereby scientists are limited to research on human embryos to a maximum of 14 days post in vitro fertilization. This rule has been in practice for many decades and was implemented on the basis that embryologically, day 14 coincides with the appearance of the primitive streak, marking the beginning of nervous system development and possible sentience.
Initially, researchers had thought the 14-day rule allowed for sufficient time to conduct adequate research as culturing conditions were unable to sustain embryos in vitro for extended periods of time. However, over the past few decades, these conditions have improved, allowing embryos to be maintained in culture beyond 14 days. This rule was implemented as a compromise for the opposing moral views regarding embryo research.
However, recently, many groups are suggesting extending the 14-day rule on the basis of technical feasibility and prospective benefits of researching unknown developmental events, postulated to significantly contribute to medical knowledge and the future of health care. Should the 14-day rule be extended and if it were, what would constitute the newly defined limits on embryo research?
Embryos used for research purposes are ultimately destined for destruction, never intended for use in establishing pregnancy. This argument is made by many groups in favour of extending the 14-day rule, claiming that the outcome for the embryo will remain unchanged, regardless of time limits allowed for research. Although technically factual, this logic is morally problematic in its reasoning, suggesting destruction of human embryos is not synonymous with extinguishing of life, regardless of time constraints to facilitate research (Nwigwe 2019).
Although the fate of the embryo does not change with extension of any time limit, from the perspective of a deontologist, the intrinsic moral status of an embryo is equivalent to that of any human being, beginning at the moment of conception. Research conducted for any purpose leading to destruction and disposal of the embryo would not be considered ethically sound as the ends do not justify the means (Nwigwe 2019). Furthermore, in the words of Immanuel Kant, each agent - the embryo in this case - should be treated not merely as a means to an end but as an end in themselves. The deontological approach is heavily based on the action which leads to an ethically relevant outcome, whereby using a human embryo as a means to an end, would be considered a morally impermissible action (Nwigwe 2019). From a gradualist viewpoint, the moral value of the embryo increases with each day of development as new structures emerge (Hurlbut et al. 2017). Therefore, extending the 14-day rule means that at the time the embryo is discarded, it will be of higher moral status, with higher potential to develop into a human being (Sawai et al. 2020).
The true ethical dilemmas in extending the 14-day rule lie in the opposing views of those, such as deontologists and gradualists, who accord the embryo with various levels of moral status, to others who perceive morality and the onset of human life differently, considering an embryo to be nothing more than a cluster of cells.
One of the most prominent arguments in favour of extending the 14-day rule revolves around the view of this ethical boundary acting as an impediment to research progress and the importance of its extension to advances in scientific knowledge and human health. This argument takes a strongly utilitarian perspective, believing that research done on human embryos further in development may lead to the discovery of new developmental moments, providing the greatest benefit for the greatest number (McCully 2021). This view implies that any harm imposed upon embryos during extended periods of research is outweighed by the medical breakthroughs that may potentially be discovered (Nwigwe 2019). This reasoning, however, is largely optimistic, simply technical and a direct violation of beneficence and non-maleficence, relying on the assumption that all embryo research is definitively progressive, overemphasizing only the potential benefits at the expense of developing personhood (Chan 2017).
This notion extends from philosopher David Hume, stating that a definitive conclusion cannot be drawn from a factual claim (Cavaliere 2017). This is known in philosophy as the ‘is/ought’ distinction. Although technically feasible, the extended maintenance of the embryo in vitro does not automatically confer beneficence to outweigh the importance of non-maleficence. The one-sided focus on the probable benefits gained from continuing research past 14 days does not consider the aspect of maleficence imposed on the developing autonomy of the embryo along with the implications to a complex pluralistic society. If the limit were to be extended, the question now becomes, to what point? There lies a great deal of ethical tension in setting a new time limit for embryo research, bringing about the possibility of a morally problematic slippery slope in which society may begin to descend (Chan 2017).
The 14-day rule itself was implemented as an ethically sound compromise between two opposing perspectives on morality involving embryo research. Allowing extension of the 14-day rule may undermine its initial purpose and facilitate progression toward further moral decline and unethical practices.
This includes development of technologies intended for germline editing or research on fetuses and potentially neonates, claiming the scientific advances gained by society, or beneficence, outweigh any possibility of harm (Appleby and Bredenoord, 2018). A continuous extension of the limit may engender discordance and lack of confidence between the members of society and those responsible for implementing new scientific policies. Researchers will continually express compelling desires to further enhance research, continuously pushing the boundaries of ethical practices, negating the autonomy of individuals within society and their complex views on the beginnings of moral personhood (Hurlbut et al. 2017). The extension of the limit also suggests scientists hold higher value to the possibility of beneficial research than respect for a just and diverse society as a whole (Matthews et al. 2021).
In a complex value plural society, a wide range of views exist regarding the moral status of the embryo, which must be respected. In addition to the concept of gradualism, by day 14, the embryo has undergone individuation, meaning the ability no longer exists to undergo spontaneous cleavage and develop into twins or higher order multiples. With the onset of individuation, in addition to the heightened moral status of the embryo, there is an increased potential for personhood and progression toward an autonomous individual, increasing the moral significance of the 14-day rule (Hyun et al. 2016). The utilitarian perspective, holding high regard for potential beneficence as the greatest outcome for society, disregards the autonomy of the developing embryo, which may be viewed as definitively established after individuation (Nwigwe 2019). In addition to individuation, there must exist a level of respect for those that attribute different events within development to differing levels of significance (Hurlbut et al. 2017). There exists a societal cost and risk of injustice to extending the limits on embryo research, whereby those who believe the embryo holds full moral status are devalued by the scientific community.
One of the most significant perspectives within society concerns the autonomy of the patient, as without consent from those who donate, embryo research would not be possible. In order for human embryos to be used for research purposes, both the genetic male and female donors contributing to the creation of the embryo must provide informed consent (Nwigwe 2019). While patients are autonomous in their decision to donate reproductive material and fully informed that any donated materials will not be used to establish pregnancy, there still exists a level of discomfort with the extension of the already existing 14-day rule. While gametes and embryos are donated, patients attach a significant degree of moral status due to the fact that there is potential to create a human being containing part of their own identity (Davis 2019). The ethical tension from the perspective of the patient concerning research on embryos beyond 14 days stems from the idea of individuation. Once past this point, the patient, viewing the embryo as a moral entity, may see the potential for personhood to have significantly increased (Davis 2019).
The ethical debates surrounding the 14-day rule, while extending from the fundamental opposing views of morality regarding embryos, have largely shifted to the technical feasibility of culturing past the current set limit (Cavaliere 2017). In addition to the technological abilities, there has also been a transition in arguments concerning beneficence of research beyond the 14-day mark, claiming that the restriction on conducting research due to the views of a complex pluralistic society would be morally impermissible (Cavaliere 2017). However, those against extending the 14-day rule hold a higher regard for human morality and the onset of personhood from the moment of conception, gradually increasing with development, as well respecting the views of a pluralistic society. The ethical strain in the extension of the 14-day rule arises in the differing views of embryo research from deontologists and utilitarians. The resolution of such a convoluted moral dilemma requires a golden mean between such extremes, utilizing a virtue ethics approach, which currently exists as the ethical limit of the 14-day rule. The most salient factor to consider lies in knowing that although technological advances over the recent years make it feasible to maintain an embryo past 14 days in vitro, it does not establish ethical permissibility.
Appleby J., Bredenoord A. (2018). Should the 14-day rule for embryo research become the 28-day rule? EMBO Molecular Medicine. 10(9): e9437. https://doi.org/10.15252/emmm.201809437
Cavaliere G. (2017). A 14-day limit for bioethics: the debate over human embryo research. BMC Medical Ethics. 18:38. https://doi.org/10.1186/s12910-017-0198-5
Chan S. (2017). How to Rethink the Fourteen-Day Rule. Policy and Politics. 47(3): 5-6. https://doi.org/10.1002/hast.698
Davis C. (2019). The Boundaries of Embryo Research: Extending the Fourteen Day Rule. Bioethical Inquiry.16:133-140. https://doi.org/10.1007/s11673-018-09895-w
Hurlbut J., Hyun I., Levine A., Lovell-Badge R., Lunshof J., Matthews K., Mills P., Murdoch A., Pera M., Scott C., Tizzard J., Warnock M., Zernicka-Goetz M., Zhou Q., Zoloth L. (2017). Revisiting the Warnock Rule. Nature Biotechnology. 35(11): 1029-1042. https://doi.org/10.1038/nbt.4015
Hyun I., Wilkerson A., Josephine J. (2016). Embryology policy: Revisit the 14-day rule. Nature. 533: 169-171. doi:10.1038/533169a
Matthews K., Iltis A., Marquez N., Wagner D., Robert J., Melo-Martin I., Bigg M., Franklin S., Holm S., Metzler I., Mole M., Taupitz J., Testa G., Sugarman J. (2021). Rethinking Human Embryo Research Policies. Hastings Center Report. 51(1): 47-51. https://doi.org/10.1002/hast.1215
McCully S. (2021). The time has come to extend the 14-day limit. Journal of Medical Ethics. 0: 1-5. doi:10.1136/ medethics-2020-106406
Nwigwe L. (2019) Embryonic Stem Cell Research: An Ethical Dilemma. Voices in Bioethics, (5). https://doi.org/10.7916/vib.v5i.6135
Sawai T., Minakawa T., Pugh J., Akatsuka K., Yamashita J., Fujita M. (2020). The moral status of human embryo-like structures: potentiality matters? Science and Society. 21(8): e50984. https://doi.org/10.15252/embr.202050984