• Robb G. Best

The Science of "Mini-brains"


What makes the human brain so, well, human?

It’s not purely a matter of size—from studying the cranial cavities of Neanderthals, we know that our bygone genetic cousins sported more gray matter than us. But seemingly that wasn’t enough to put them in the same ecological niche, or even just to keep them from extinction.

After close examination and a lot of theorizing, researchers at Oxford have suggested that the main brain difference between them and us was more a matter of function, that Neanderthal brains prioritized muscle control and eyesight while ours focused more on developing the social skills necessary to form a tight-knit group. In other words, maybe the human brain’s main asset is the ability to foster teamwork.

It’s a nice thought, even if it is unprovable: other scientists have proposed many other theories for the disappearance of the Neanderthal, including interspecies breeding that simply blended them into humans, or even a matter of simple geography. And a number of living creatures have larger brains than us, including elephants and dolphins.

So why are we the ones with computers and lattes and jazz music? Given that we are all animals, what does the human brain do differently? How does it develop those differences? And given that you can’t put a developing fetal brain under a microscope or in an fMRI, how can we ever hope to study this?

Enter the vat-grown brain.

Don’t worry, you don’t have to picture an entire human brain floating in a jar like something from a cartoon. Instead, these “organoids” or “minibrains” are wads of lab-developed brain tissue, the product of white blood cells triggered into forming stem cells. And Science magazine reports that researchers are already using these wads of tissue for some interesting studies.

At a recent symposium in the Netherlands, neurobiologist Wieland Huttner of the Max Planck Institute of Molecular Cell Biology and Genetics described one such experiment. Huttner’s team wanted to figure out which substances produce the first brain folds in a human fetus. After searching the databases for genes that express themselves at the right period of development (roughly 20 week)s, they hit upon three specific proteins. Added to the organoid, this trio of proteins made the tissue form folds of its own. A postdoc named Katie Long noticed that a molecule called hyaluronic acid also seemed to be a necessary component—surprising, since nobody had realized hyaluronic acid was so important to early brain development.

Since you can’t exactly put a developing fetal brain under a microscope and watch it in real-time, or legally obtain a chimp brain (their dwindling numbers make them a protected species), access to growing blobs of brain tissue can be a pretty exciting prospect. "We used to be just limited to looking at sequence data and cataloging differences from other primates," says neurogeneticist Simon Fisher. "Now, we have these exciting new tools that are helping us to understand which genes are important."

Will organoids prove to be a starring player in the history of brain science? Or will they turn out to be an overhyped fad, years from yielding useful results, like vat-grown steaks? Only time—and science—will tell.


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