All great scientific advances have a way of exposing the imprecision of common concepts and forcing people to rethink them.
John Aach
Abstract
Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the “gastruloid,” which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos. But fitting an ambiguous object into an existing category with well-worn pathways in research ethics, like the embryo, is only a temporary fix. The bigger problem is that we no longer know what an embryo is. We haven’t had a non-absurd definition of ‘embryo’ for several decades and without a well-defined comparison class, asking whether gastruloids belong to the morally relevant class of things we call embryos is to ask a question without an answer. What’s the alternative? A better approach needs to avoid what I’ll refer to as “the potentiality trap” and, instead, rely on the emergence of morally salient facts about gastruloids and other synthetic embryos.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
Gastruloids belong to a growing category of Synthetic Human Entity with Embryo-like Features (SHEEFs), an acronym coined by Aach et al. (2017).
Throughout the paper, I’ll be using ‘embryo’ instead of ‘human embryo’ for the sake of brevity.
Part of the interest in the question surely arises because the answer influences how these entities will be regulated. If gastruloids were considered embryos, they would be subject to the 14-day rule. In more than a dozen countries—including the U.S.—in vitro research on human embryos is restricted to the first 14 days of development, or the period before the appearance of the primitive streak. Recently, scientists managed to sustain human embryos in vitro for 12–13 days (Deglincerti et al. 2016; Shahbazi et al. 2016)—almost double the duration of what’s been possible prior to 2016—and this success has prompted requests to extend or at least revisit the 14-day rule. But whatever the limit ends up being, the relevant point for our purposes is that it will also apply to the gastruloid. That is, if gastruloids are functionally akin to human embryos, on the basis of that resemblance they’re likely to be subject to whatever research restrictions apply to human embryos.
The claim I’m here making has implications for the moral status of “regular” embryos. I’ll not be engaging those implications here. Instead, I aim to focus exclusively on the moral status of synthetic embryos.
For the legal and regulatory struggles of trying to define ‘embryo’ in the last 20 years, see Baylis and Krahn (2009), Cameron and Williamson (2005), de Miguel-Beriain (2014, 2015), Maienschein (2002), Pera et al. (2015), Peters (2006), Piciocchi and Martinelli (2016), and Stanton and Harris (2005).
Typically, it is ‘persons’ who are afforded special moral status. As a rule of thumb, all human beings are assumed to be persons and only with considerable argumentation will that status be revoked. At death, for example, an individual may stop being a person, even if he is still a human being. It’s on this basis, presumably, that post-mortem autopsies are ethical. Some non-humans may be persons (God, the angels, and corporations, perhaps) but generally, non-human members of the animal kingdom are assumed not to be persons. It’s for this reason (again presumably) that experimentation on mice, monkeys, and a host of other animals is permitted.
Another problem with the argument from potentiality that I will not focus on is the obvious non-sequitur. It does not follow from A’s being a potential B that A should be treated as B (see, Testa et al. 2007, pp. 154–155). For example, the popsicle I’m eating has the potential to be a puddle on the floor, but I shouldn’t start licking the floor because of that fact.
Another way to argue that potential is inherently teleological is to tie it to natural selection. McGee, for example, characterizes an entity’s potential as “what the entity has been designed by natural selection to do, what it does, or is for, once it reaches maturity” (2014, p. 697).
“Totipotency” is typically defined as a cell’s potential to produce a whole organism and, in mammals, its associated membranes, e.g., a placenta.
Condic argues that totipotency is a property of the single-celled embryo up to the four-cell stage of embryonic development. So ‘embryo,’ as I’m using it in the context of Condic’s view, refers to any cell up to the four-cell stage.
That is, scientists have been inducing potency in cells with a more complicated environment—that of a tetraploid embryo—for some time. The procedure is known as tetraploid complementation (or tetraploid sandwich) and involves fusing two cells from the first cell division after fertilization into one cell (with four complete sets of chromosomes, hence the name “tetraploid”). The big, fused cell then grows into a blastocyst. If cells that have the potency equivalent of hESCs are injected into this teraploid blastocyst, and the “blastocyst sandwich” is implanted in a uterus, the embryo proper will form entirely from the injected hESCs. The teraploid cells contribute only to the extraembryonic membranes and placenta. Hence, since the invention of the tetraploid complementation procedure in 1990, scientists have known that cells can gain the potency of being able to create all cells of the body and to self-organize if added to other cells, i.e., to the tetraploid blastocyst.
McGee (2014) uses “enabling” and “disabling” conditions in lieu of Denker’s “instructive” and “destructive” environments. In contrast to Denker, however, he also argues that the embryo has a true intrinsic potential that can be helped or hindered by these conditions. I disagree with McGee. The fact that en embryo’s potential is context-dependent means that there is no such thing as a neutral environment in which we can judge the embryo’s true intrinsic potential.
Whether hESCs or hiPSCs could actually grow into human beings has never been tested. Indeed, as Fagan has argued, the evidential constraints of these tests entail that “hypotheses about stem cell capacities (self-renewal and differentiation potential) can never be fully and decisively established by experiments” (2013, p. 956). My claim, then, that hESCs or hiPSCs could develop in this way rests on the idea that they exhibit properties scientists believe are indicative of having such potential. And, in anyway, all I need to show is that embryos don’t have the potential uniquely, which I’ve done.
References
Aach, J., J. Lunshof, E. Iyer, and G. Church. 2017. Addressing the ethical issues raised by synthetic human entities with embryo-like features. eLife. https://doi.org/10.7554/elife.20674.
Baertschi, B., and A. Mauron. 2010. Moral status revisited: The challenge of reversed potency. Bioethics 24 (2): 96–103.
Baylis, F., and T. Krah. 2009. The trouble with embryos. Science Studies 22: 31–54.
Cameron, C., and R. Williamson. 2005. In the world of Dolly, when does a human embryo acquire respect? Journal of Medical Ethics 31: 215–220.
Campbell, K.H., J. McWhir, W.A. Ritchie, and I. Wilmut. 1996. Sheep cloned by nuclear transfer from a cultured cell line. Nature 380 (6569): 64–66.
Condic, M.L., P. Lee, and R.P. George. 2009. Ontological and ethical implications of direct nuclear reprogramming: Response to Magill and Neaves. Kennedy Institute of Ethics Journal 19 (1): 33–40.
Condic, M. 2014. Totipotency: What it is and what it is not. Stem Cells and Development 23 (8): 796–812.
Damjanov, I., and D. Solter. 1974. Experimental teratoma. In Current topics in pathology. Current topics in pathology (Ergebnisse der Pathologie), vol. 59, ed. E. Grundmann and W.H. Kirsten. Berlin: Springer.
Deglincerti, A., G.F. Croft, L.N. Pietila, M. Zernicka-Goetz, E.D. Siggia, and A.H. Brivanlou. 2016. Self-organization of the in vitro attached human embryo. Nature, 533 (7602): 251. Retrieved from, http://link.galegroup.com/apps/doc/A463709146/AONE?u=albanyu&sid=AONE&xid=7b8dcdda.
De Miguel Beriain, I. 2014. What is a human embryo? A new piece in the bioethics puzzle. Croatian Medical Journal 55 (6): 669–671. https://doi.org/10.3325/cmj.2014.55.669.
De Miguel-Beriain, I. 2015. The ethics of stem cells revisited. Advanced Drug Delivery Reviews 82–83: 176–180.
Denker, H.W. 2014. Stem cell terminology and ‘synthetic’ embryos: A new debate on totipotency, omnipotency, and pluripotency and how it relates to recent experimental data. Cells Tissues Organs 199: 221–227.
Devolder, K., and J. Harris. 2007. The ambiguity of the embryo: Ethical inconsistency in the human embryonic stem cell debate. Metaphilosophy 38: 153–169.
Fagan, M.B. 2013. The stem cell uncertainty principle. Philosophy of Science 80: 945–957.
Fagan, M. 2017. Stem cell lineages: Between cell and organism. Philosophy, Theory, and Practice in Biology 9 (6): 1–23.
Harman, E. 2003. The potentiality problem. Philosophical Studies 114: 173–198.
Harris, J. 1985. The value of life: An introduction to medical ethics. Boston: Routledge & Kegan Paul.
Hurlbut, J.B., I. Hyun, A.D. Levine, R. Lovell-Badge, J.E. Lunshof, K.R.W. Matthews, et al. 2017. Revisiting the Warnock rule. Nature Biotechnology 35 (11): 1029–1042.
Hyun, Insoo, Wilkerson Amy, and Josephine Johnston. 2016. Embryology policy: Revisit the 14-day rule. Nature 533 (7602): 169–171.
Jarvis, G.E. 2016. Early embryo mortality in natural human reproduction: What the data say. F1000Research 5: 2765.
Magill, G. and W.B. Neaves. 2009. Ontological and ethical implications of direct nuclear reprogramming. Kennedy Institute of Ethics Journal 19 (1): 23–32. Johns Hopkins University Press. Retrieved March 24, 2018, from Project MUSE database.
McGee, A. 2014. The potentiality of the embryo and the somatic cell. Metaphilosophy 45: 689–706.
Maienschein, J. 2002. What’s in a name: Embryos, clones, and stem cells. The American Journal of Bioethics 2 (1): 12–19.
Nuffield Council on Bioethics. 2017. Human embryo culture. London: Nuffield Council on Bioethics.
Pera, M.F., G. de Wert, W. Dondorp, R. Lovell-Badge, C.L. Mummery, M. Munsie, and P.P. Tam. 2015. What if stem cells turn into embryos in a dish? Nature Methods 12 (10): 917–919.
Peters Jr., P.G. 2006. The ambiguous meaning of human conception. University of California. Davis Law Review 40: 199.
Piciocchi, C., and L. Martinelli. 2016. The change of definitions in a multidisciplinary landscape: The case of human embryo and pre-embryo identification. Croatian Medical Journal 57 (5): 510–515. https://doi.org/10.3325/cmj.2016.57.510.
Regalado, A. 2017. Artificial human embryos are coming and no one knows how to handle them. MIT Technology Review. https://www.technologyreview.com/s/608173/artificial-human-embryos-are-coming-and-no-one-knows-how-to-handle-them/.
Rivron, N.C., J. Frias-Aldeguer, E.J. Vrij, J.C. Bolsset, J. Korving, J. Vivie, et al. 2018a. Blastocyst-like structures generated solely from stem cells. Nature 557 (7703): 106–111.
Rivron, N.C., M. Pera, J. Rossant, Arias A. Martinez, M. Zernicka-Goetz, J. Fu, et al. 2018b. Debate ethics of embryo models form stem cells. Nature 564 (7735): 183–185.
Sagan, A., and P. Singer. 2007. The moral status of stem cells. Metaphilosophy 38: 264–284.
Shahbazi, M.N., A. Jedrusik, S. Vuoristo, G. Recher, A. Hupalowska, V. Bolton, N.N.M. Fogarty, A. Campbell, L. Devito, D. Ilic, Y. Khalaf, K.K. Niakan, S. Fishel, and M. Zernicka-Goetz. 2016. Self-organisation of the human embryo in the absence of maternal tissues. Nature Cell Biology 18 (6): 700–708. https://doi.org/10.1038/ncb3347.
Shahbazi, M.N., and M. Zernicka-Goetz. 2018. Deconstructing and reconstructing the mouse and human early embryo. Nature Cell Biology 20: 878–887.
Sherman, M.I., and D. Solter. 1975. Teratomas and differentiation. New York: Academic Press.
Stanton, C., and J. Harris. 2005. The moral status of the embryo post-Dolly. Journal of Medical Ethics 31 (4): 221–225. https://doi.org/10.1136/jme.2004.008086.
Stier, M., and B. Schoene-Seifert. 2013. The argument from potentiality in the embryo protection debate: Finally “depotentialized”? American Journal of Bioethics 13 (1): 19–27.
Takahashi, K., K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka. 2007. Induction of pluripotent stem cells form adult human fibroblasts by defined factors. Cell 131 (5): 861–872.
Testa, G., L. Borghese, J.A. Steinbeck, and O. Brustle. 2007. Breakdown of the potentiality principle and its impact on global stem cell research. Cell Stem Cell 1 (2): 153–156.
Thomson, J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall, and J.M. Jones. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282 (5391): 1145–1147.
Tooley, M. 1974. Abortion and Infanticide. In The rights and wrongs of abortion, ed. Marshall Cohen, Thomas Nagel, and Thomas Scanlon. Princeton: Princeton University Press.
Warmflash, A., B. Sorre, F. Etoc, E.D. Siggia, and A.H. Brivanlou. 2014. A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nature Methods 11 (8): 847–854. https://doi.org/10.1038/nmeth.3016.
Xu, P.F., N. Houssin, K.F. Ferri-Lagneau, B. Thisse, and C. Thisse. 2014. Construction of a vertebrate embryo from two opposing morphogen gradients. Science 344: 87–89.
Acknowledgements
Thanks to Gunnar Babcock, Jake Earl, Insoo Hyun, P.D. Magnus and most of all to Matt Mosdell, for helpful discussion and feedback on earlier drafts.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Piotrowska, M. Avoiding the potentiality trap: thinking about the moral status of synthetic embryos. Monash Bioeth. Rev. 38, 166–180 (2020). https://doi.org/10.1007/s40592-019-00099-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40592-019-00099-5