Today in @Nature, we report a new approach to studying human brain development and modeling disease in vivo. Human neural #assembloids and #organoids have opened new ways to study development in vitro, but they also have important limitations. Transplantation can provide a more physiological environment, yet human cortical cells then develop within a rodent brain that matures much faster, constraining their growth and integration. To address some of these limitations and obtain more advanced functional readouts relevant to disease biology, we generated #apallial mice, in which ~98% of the cortex and hippocampus fail to form, creating space for transplanted human cortical organoids to grow and integrate extensively. We call these #xenocortical mice (XCX). Nearly 7 years in the making. Congratulations to an extraordinary team and wonderful collaborators! Link to the article below 👇

Today in @Nature, we report a new approach to studying human brain development and modeling disease in vivo. Human neural #assembloids and #organoids have opened new ways to study development in vitro, but they also have important limitations. Transplantation can provide a more physiological environment, yet human cortical cells then develop within a rodent brain that matures much faster, constraining their growth and integration. To address some of these limitations and obtain more advanced functional readouts relevant to disease biology, we generated #apallial mice, in which ~98% of the cortex and hippocampus fail to form, creating space for transplanted human cortical organoids to grow and integrate extensively. We call these #xenocortical mice (XCX). Nearly 7 years in the making. Congratulations to an extraordinary team and wonderful collaborators! Link to the article below 👇

Today in 🤯 science: A team led by @Sergiu_P_Pasca engineered mice to be missing a large swath of their brains. Next, they transplanted human brain organoids, which grew and filled in the void. They're still mice, but with a human-dominated cortex. nytimes.com/2026/09/16/scien…

In an extraordinary new paper, just out, in Nature @Sergiu_P_Pasca and his team genetically altered mice to make them "apallial" (missing a cortex). And then, postnatally, transferred organoids derived from human neural cells into that space. Three months later, in the animals measured, the cortex was 91.9% human-derived neural cells by volume. The result is not quite a mouse mouse (albeit I would still say, it's a mouse!), and certainly not anything like a human. Nothing the researchers measured suggests these animals have human-like experiences. What a model like this promises for neurological disease modeling and drug discovery cannot be overstated. It's nothing short of an extraordinary breakthrough. It also raises complex ethical questions (to be clear, these researchers carefully engaged external ethicists (I was one of them), and followed every ethical and legal guideline possible.) Which is why In a forthcoming commentary, Anil Seth and I explore what an ethical roadmap forward would be for this work. We address whether these mice chimeras could have any human-like capacities, how we might measure and know, and who, and how, we decide together what the next steps in this research should be.

An extraordinary @Nature paper has just landed from the lab of @Sergiu_P_Pasca at @Stanford - led by Konstantin Kaganovsky. They have found a way to create "xenocortical mice" which have ~92% of their cortex occupied by a cortical organoid derived from human stem cells. This human-derived cortical graft integrates deeply with the host nervous system, supporting organised neural activity and behaviour. This study is a milestone in synthetic biology and chimera research. It has the potential to generate multiple medical breakthroughs by providing an enhanced biological model of human brain tissue that allows behavioural as well as neural and genetic assays. The Stanford team have been exceptionally thorough and proactive in addressing ethical concerns that comes from this frontier work. But their pioneering work nonetheless raises many open questions: are the xenocortical mice conscious? Do they have any human-like properties of consciousness or cognition? @NitaFarahany and I will be addressing some of these questions in a forthcoming commentary - where we'll also offer an ethically-informed roadmap to guide this important research as it progresses. In this context, "pacing the frontier" really does make sense 😉 Read the Stanford @nature paper here, and buckle up. It's wild. nature.com/articles/s41586-0…