Five-Year-Old Mini Brains Can Now Mimic a Kindergartener’s Neural Wiring. It’s Time to Talk Ethics.

When brain organoids were introduced roughly a decade ago, they were a scientific curiosity. The pea-sized blobs of brain tissue grown from stem cells mimicked parts of the human brain, giving researchers a 3D model to study, instead of the usual flat layer of neurons in a dish.

Scientists immediately realized they were special. Mini brains developed nearly the whole range of human brain cells, including neurons that sparked with electrical activity, making them an excellent way to observe and study the human brain—without the brain itself.

As the technology advanced and brain organoids matured, researchers coaxed them to grow structural layers with blood vessels roughly mimicking the cortex, the part of the brain that handles reasoning, working memory, and other high-level cognitive tasks. Parallel efforts derived organoids for other parts of the brain.

Mini brains can be made from a person’s skin cells and faithfully carry the genetic mutations that could cause neurodevelopmental disorders, such as autism. The lab-grown blobs also provide a nearly infinite source of transplantable neural tissue, which in theory could help heal the brain after a stroke or other traumatic events. In early studies, organoids transplanted into rodent brains formed neural connections with resident brain cells.

More recently, assembloids have combined mini brains with other tissues, like muscles or blood vessels. These Frankenstein-ish assemblies capture how the brain controls bodily functions—and when those connections go awry.

As brain organoids have grown increasingly complex, ethical concerns about their use have grown too. After all, they’re made of neural tissue, which in our heads forms the basis of memory, emotions, sensations, and consciousness.

To be clear, there’s no evidence brain organoids can think or feel. They are absolutely not brains in a jar. But scientists can’t ignore the possibility they could eventually develop some sort of “sensation,” such as pain and, if they do, what that might mean for their development.

Aging Organoids

Harvard’s Paula Arlotta is among those who are concerned. An expert in the field, her team has developed ways to keep brain organoids alive for an astonishing seven years. Each nugget, smaller than a pea, is jam-packed with up to two million neurons and other human brain cells.  

Studying these mini brains for years has delivered an unprecedented look into human brain development. Our brains take nearly two decades to mature, an exceptionally long period of time compared to other animals. As the team’s organoids aged, they slowly changed their wiring and gene expression, reports Arlotta and colleagues in a recent preprint.

In older organoids, progenitor cells—these are young cells that can form different types of brain cells—quickly decided what type of brain cell they would become. But in younger organoids, the same cells took time to make their decision. As the blobs grew over an astonishing five years, their neurons matured in shape, function, and connections, similar to those of a kindergartner.

These long-lasting organoids could reveal secrets of the developing brain. Some efforts are tracing the origins of different cell types and how they populate the brain. Others are generating organoids from people with autism or deadly inherited brain disorders to test treatments.

Excitement is at an all-time high. But while championing the research, Arlotta and other experts recently penned an article arguing for a global regulation committee to steer the nascent field.