Methodological note: The personal-ontological status of synthetic embryo models is deliberately kept open on this page. An earlier version had apodictically excluded SEMs from the circle of persons; this determination has been withdrawn in favour of tutiorist caution.
A synthetic embryo model (stem-cell-based embryo model, SEM; iBlastoid; blastoid; gastruloid) is an embryo-like structure artificially generated from pluripotent stem cells that has not arisen through the fertilization of egg and sperm cell. Pioneering works include:
- Liu et al. (Monash 2021): iBlastoids from reprogrammed fibroblasts
- Yu et al. (2021) / Kagawa, Rivron et al. (2022): blastoids from naive pluripotent stem cells
- Oldak / Hanna et al. (Weizmann 2023): complete post-implantation embryo models at the day-14 stage from naive embryonic stem cells
- Tarazi / Hanna Lab (2022): post-gastrulation embryos ex utero (mouse ESCs)
The ISSCR Guidelines (update May 2021, Lovell-Badge et al.) relax the classical 14-day rule for such models. The ISSCR Standards 2023 codify the pluripotency hierarchy (toti-/naive pluri-/primed pluri-/multi-/unipotent) by which ISSCR research is conceptually oriented. In its revision (Stem Cell Reports 2025), the ISSCR Embryo Models Working Group discards the previously used distinction between “integrated vs. non-integrated” SCBEMs as scientifically untenable, and constitutes the present framework of ethical assessment.
The Family of Synthetic Embryo Models
Research today recognizes several types, all of which fall under the umbrella term but differ in their mode of generation:
- Blastoid — a blastocyst-like model generated from naive pluripotent stem cells (Yu et al., Nature 591:620–626, 2021; Kagawa, Rivron et al., Nature 601:600–605, 2022).
- iBlastoid — a blastoid from reprogrammed fibroblasts (Liu et al., Nature 591:627–632, 2021).
- EPS-Blastoid — a blastoid from extended pluripotent stem cells (classificatorily captured in the ISSCR SCBEM Statement 2024).
- Gastruloid — a model of gastrulation without extra-embryonic structures.
- Post-implantation embryo model — a complete day-14 model with embryonic disc, yolk sac, and trophoblast (Oldak/Hanna et al., Nature 622:562–573, 2023; Weatherbee/Zernicka-Goetz et al., Nature 622:584–593, 2023).
This list is not exhaustive; research is advancing rapidly. From the standpoint of personal ontology, the same tutiorist basic posture holds for all of them — see below.
With the availability of the HuDeCA cell atlases (in particular Tyser/Srinivas 2021 for CS 7 and the haematopoietic and neural atlases 2019–2024), the comparison SCBEM ↔ in vivo becomes transcriptomically quantifiable for the first time: if a synthetic model recapitulates the single-cell signature of a post-gastrulation embryo, the question of its person-status can no longer be defined away morphologically — it shifts to the question of which matching criteria are sufficient. The tutiorist basic posture is thereby sharpened, not relieved.
Fact vs. Person-Status
A distinction must be drawn:
Fact — unambiguous:
Synthetic embryo models do not arise through the fertilization of egg and sperm cell.
Person-status — open:
From this it does not follow with logical necessity that a synthetic embryo model is not a human person.
Within the personal-ontological tradition (Boethius–Aquinas–Spaemann), fertilization is the typical ontological inceptive event of human existence (cf. beginning of human existence). It is, however, an epistemic surrogate for the actual ontological criterion: that a concrete individual substance of a rational nature is present, bodily actualized. So long as it cannot be reliably decided empirically whether a sufficiently developed SEM bears this nature or not, the question of personhood remains open.
The Tutiorist Approach
Where there is substantial uncertainty about the personhood of a being, the traditional principle in dubio pro persona holds (by analogy to the criminal-law principle in dubio pro reo).
This methodological caution is not an additional standard — it is the very same line that the substance-ontological concept of person brings to bear against premature exclusions (for instance in Peter Singer): whoever denies person-status to embryos, the severely demented, or the comatose because they presently display no acts of reason confuses epistemic inaccessibility with ontological non-existence.
Symmetrically: whoever prematurely denies person-status to synthetic embryo models because they have not arisen through fertilization risks the same methodological error — only in the other direction.
Consequences for Research and Law
From the openness of the person-status there follow — independently of any later empirical clarification — three cautious conclusions:
- Research-ethical caution. So long as the status is open, synthetic embryo models are not to be treated like arbitrary cell material. The ISSCR’s 2021 relaxation of the 14-day rule shifts responsibility — it does not remove it.
- Asymmetry of the burden of proof. The burden of proof lies with those who would deny personality, not with those who hold it to be possible. Premature denial is, ontologically as well as historically, riskier than premature affirmation.
- Empirical openness. Research is moving rapidly toward structures that no longer clearly fall short of the biological embryo. An apodictic ontological determination would freeze an empirical assumption that may be false tomorrow.
Ontological Classification
- is a form of: Ontologically Uncertain Status
- fact: no arising through fertilization
- deliberately no hard separation from human person or embryonic phase — precisely the avoidance of any such apodictic statement is the point of this classification
Follow-Up Questions That Remain Open
- Which empirical criteria (genome integrity, capacity for implantation, self-organization as an organism, neural anlage …) would be sufficient to ascribe personality?
- Would a being arising through cloning technique (somatic cell nuclear transfer) be ontologically closer to the embryo or to the SEM?
- When does responsibility shift from “research on a cell aggregate” to “research on a human being of unclarified status”?
These questions are not rhetorical embarrassments — they are the actual work that has to be done.
Sources: Generated by querying the Personhood ontology.
Further sources — empirical (synthetic embryo models):
- Liu, X., Tan, J. P., Schröder, J. et al. (2021): Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 591: 627–632. (Monash University, Polo Lab.)
- Oldak, B., Wildschutz, E., Bondarenko, V. et al. (2023, Hanna as corresponding author): Complete human day 14 post-implantation embryo models from naive ES cells. Nature 622: 562–573.
- Tarazi, S., Aguilera-Castrejon, A., Joubran, C. et al. (2022, Hanna Lab): Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs. Cell 185(18): 3290–3306.e25.
Further sources — HuDeCA reference atlases (benchmarking basis):
- Tyser, R. C. V.; Mahammadov, E.; Nakanoh, S.; Vallier, L.; Scialdone, A. & Srinivas, S. (2021): Single-cell transcriptomic characterization of a gastrulating human embryo. Nature 600(7888): 285–289.
- Popescu, D.-M.; Botting, R. A.; Stephenson, E.; … & Haniffa, M. (2019): Decoding human fetal liver haematopoiesis. Nature 574(7778): 365–371.
- Suo, C.; Dann, E.; Goh, I.; … Haniffa, M.; Teichmann, S. A. et al. (2022): Mapping the developing human immune system across organs. Science 376(6597): eabo0510.
- Braun, E.; Danan-Leon, M.; Hochgerner, H.; … & Linnarsson, S. (2023): Comprehensive cell atlas of the first-trimester developing human brain. Science 382(6667): eadf1226.
Further sources — research ethics (ISSCR / 14-day rule):
- Lovell-Badge, R., Anthony, E., Barker, R. A. et al. (2021): ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update. Stem Cell Reports 16(6): 1398–1408.
- Clark, A. T., Brivanlou, A., Fu, J. et al. (2021): Human embryo research, stem cell-derived embryo models and in vitro gametogenesis: Considerations leading to the revised ISSCR guidelines. Stem Cell Reports 16(6): 1416–1424.
- Hyun, Insoo, Wilkerson, Amy & Johnston, Josephine (2016): Embryology policy: Revisit the 14-day rule. Nature 533: 169–171 (key text in the immediate prehistory of the 2021 ISSCR revision; it marks the counter-position against which a tutiorist line must argue).
Further sources — personal-ontological (in dubio pro persona, burden of proof):
- Spaemann, Robert: Persons: The Difference between ‘Someone’ and ‘Something’, transl. Oliver O’Donovan, Oxford: Oxford University Press 2006 (German original 1996).
- George, Robert P. & Tollefsen, Christopher (2008): Embryo: A Defense of Human Life. New York: Doubleday (expanded ed. Witherspoon Institute, Princeton 2011). — Supports tutiorist caution along a non-religious line of argument; cf. ch. 4 (“The Argument from Potential”) and ch. 6 (“Difficult Cases”).
- Snead, O. Carter (2020): What It Means to Be Human: The Case for the Body in Public Bioethics. Cambridge, MA: Harvard University Press. — A plea for an anthropology oriented toward bodily vulnerability, connectable to Spaemann’s concept of recognition.