A two-tier framework for responsible research on human embryo models.
De Los Angeles A., Bayne T., Benvenisty N., Deng H., Fujita M., Ji W., Latham S., Li T., Liu P., Loh Y-H., Lunshof J., Pei D., Pho N., Silva JCR., Ka Ki Tam TT., Tao T., Trounson A., Xu S., Yu L., Koplin J., Regenberg A., Sugaya K., Savulescu J., Zernicka-Goetz M., Lovell-Badge R.
Human stem-cell-based embryo models (SCBEMs) imperfectly mimic some-but not all-features of early human development. Yet as these models become increasingly sophisticated, they raise important ethical and regulatory questions. Despite their limitations, SCBEMs already offer powerful platforms to study human embryology, infertility, reproduction, and regenerative medicine. To avoid restrictions that could stall progress for decades, it is essential to proactively establish a clear regulatory framework-one that protects public trust without inhibiting scientific progress. We propose a two-tiered oversight structure anchored in a single fixed ethical principle: no SCBEM should ever attain the capacity for sentience (the ability to experience sensory inputs, such as pain). Tier 1 sets a developmental limit at two criteria: neural tube closure or the appearance of both a defined number of somites and limb buds, corresponding to ∼Day 28 post-fertilization analogue (PFA). Tier 2 allows research requiring a higher level of oversight up to Day 56 PFA, remaining well before the earliest debated threshold of sentience. This framework provides proportionate oversight and enforceable boundaries while acknowledging that concerns beyond sentience will persist for some stakeholders. Our goal is to prepare responsibly for the future, when the models become improved, enabling discovery without compromising ethical integrity.