Organoids: why 3D cell aggregates haven't transformed drug discovery

In a recent LessWrong essay, Abhishaike Mahajan tackles a deceptively simple question: why aren't organoids—lab-grown 3D human tissues—already replacing animal models and clinical trials in drug discovery? The answer, he argues, lies in the field's foundational identity crisis. Mahajan notes that common definitions of organoids are so broad they could include blood clots, teratomas, and biofilms. A 2014 Science review tightened this by requiring stem cell origin, multiple organ-specific cell types, and organ-specific function, but even that fails to separate pluripotent stem cell (PSC) organoids from tissue stem cell (TSC) organoids. PSC organoids recapitulate developmental biology, while TSC organoids mimic adult tissue homeostasis—two fundamentally different systems lumped under one label.

This ambiguity has practical consequences. Without clear classification, validation and quality control are nearly impossible, and assay reproducibility suffers. Spheroids—simple 3D cell aggregates that lack tissue architecture—are often marketed as organoids, further muddying the sink. Mahajan doesn't dismiss the technology's potential, but he argues that the field must first standardize its terminology and protocols before organoids can deliver on their promise of accelerated, human-relevant drug testing. His piece is a call for rigor: define what you're actually growing, then organoids may earn their place in pharma's toolkit.