Scientists Grew Tiny Human Forebrains in a Dish

The so-called organoids could shed light on how autism and schizophrenia develop

Human forebrain organoids in a cell culture dish. Credit: Pasca Lab, Stanford University

Studying how the human brain develops is difficult. Brain tissue can’t be removed from living people, and although it can be examined after someone dies, dead organs are not ideal for studying the mechanisms that give rise to brain disorders. Animal brains can only tell scientists so much, and human fetal tissue is hard to come by.

As an alternative to real brain tissue, researchers have recently figured out how to turn stem cells into neurons and grow them until they form tiny, three-dimensional blobs of brain tissue no bigger than a pea. Now, these aren’t actual human brains, of course — they’re just models. But they do mimic certain characteristics of the human brain at a very rudimentary level. Scientists call them brain organoids.

Scientists have created organoids of different brain regions — such as the midbrain and hippocampus — and all appear to have genetic similarities to human brains. Now, investigators at Stanford University and the Chan Zuckerberg Biohub, founded in 2016 with $600 million from Facebook CEO and founder Mark Zuckerberg and his wife Priscilla Chan, have created organoids that imitate the human forebrain in a petri dish. The forebrain is the largest part of the brain and is responsible for many of our most uniquely human traits, including thinking, perceiving, and evaluating sensory information. In a new paper in Science, the researchers say their organoids accurately model late stages of brain development.

Fluorescent close-up of a brain organoid showing different cell types in light green. Credit: Pasca Lab, Stanford University

To make the organoids, researchers started with human induced pluripotent stem cells — adult cells that have been reverted to an embryonic-like state and can be differentiated into any cell type. The team clumped together these stem cells using a mixture of chemicals and growth factors and then coaxed them into different types of neurons found in the forebrain. They were able to keep the organoids alive for nearly 600 days.

The researchers used these tiny forebrain models to generate a map of chromatin — the material that is wrapped around DNA, RNA, and proteins — and found that the chromatin patterns in the organoids were similar to those found in real human brain tissue. They also used the organoids to identify genes linked to autism and schizophrenia and the kinds of cells in which these genes were “turned on.” The results point to a promising way to investigate neurodevelopmental disorders.

A close-up of brain organoids in a cell culture dish. Credit: Pasca Lab, Stanford University

Don’t worry — it won’t be possible to create a full-sized human brain in the lab anytime soon. The brain organoids that scientists have managed to grow so far lack many cell types found in a real brain as well as certain neural connections that are necessary for higher brain function. Still, some experts worry about brain organoids becoming too humanlike.

In October, a group of scientists at the University of California, San Diego, created brain organoids that generated electrical patterns similar to brain waves observed in premature infants. It was the first such brain activity that had been shown in lab-grown organoids.

Some researchers have also transplanted human brain organoids into rodents, raising concerns that lab animals could develop humanlike self-awareness and consciousness. H. Isaac Chen, a neurosurgeon at the University of Pennsylvania’s Perelman School of Medicine, and his colleagues published a paper in October alongside the UC San Diego study calling on scientists to come up with ethical guidelines for using brain organoids for research, including transplanting them into animals.

“Such guidelines can help avoid confusion for scientists, especially when communicating with the public, and clearly lay out the benefits of this research, against which any ethical or moral risks can be weighed,” Chen said in a statement. “While today’s brain organoids and brain organoid hosts do not come close to reaching any level of self-awareness, there is wisdom in understanding the relevant ethical considerations in order to avoid potential pitfalls that may arise as this technology advances.”

Former staff writer at Medium, where I covered biotech, genetics, and Covid-19 for OneZero, Future Human, Elemental, and the Coronavirus Blog.

Get the Medium app

A button that says 'Download on the App Store', and if clicked it will lead you to the iOS App store
A button that says 'Get it on, Google Play', and if clicked it will lead you to the Google Play store