Scientists Are Modeling Disease in Test-Tube Brains Grown From Stem Cells

The problem with neurological research is that the brain is kind of a tough organ to study without, you know, killing someone. And the human brain is so advanced that studying diseases like Parkinson's and Alzheimer's in mice and primates doesn't really cut it. Except now, there are indications that scientists might be able to grow "mini brains," or "organoids" in test tubes.

It sounds like the start to a dystopian sci-fi flick, but it's already happening, and social conservatives are sure to be thrilled about it. Earlier this summer, researchers at the Institute of Molecular Biology in Vienna were able to take stem cells derived from skin and turn them into brains that are similar to those of a fetus nine weeks into its development.

That study was published in Nature in late August. At the time, Clive Svendsen, a neurobiologist at UCLA, told Nature that the work was "a seminal study to making a brain in a dish." Two months later, other neuroscientists are dreaming even bigger. In a paper published Thursday in Science, Harvard researcher Christopher Walsh writes that the rudimentary brains are "heralding a new phase of modeling human disease."

"You simply cannot analyze human brain development directly," he wrote. Brain scans and postmortem dissections are helpful, but give scientists an incomplete picture of what's really going on within the brain. Mice—with a cerebral cortex one-thousandth the size of a human's—make OK models for some diseases, poor models for others. "The more we try to model human disease in the mouse … the more we recognize the limitations of animal models."

Mini brains, on the other hand recreate "a surprising number of features of human embryonic brain development," he suggests.

The key to the whole thing is the fact that stem cells, when grown in this manner, produce structures that are similar to precursors of the eyes, pituitary glands, and other important brain structures. What's more, the specialized regions of these "brains" form in as little as 20 days. In normal fetuses, it can take months.

Just how "mini" are these brains? Very.

A lack of blood supply limits them to roughly 4 millimeters in diameter, and they do not produce all of the structures needed for normal brain function. It's unclear if it will be possible to use organoids to model diseases such as Alzheimer's, Parkinson's, and Chronic Traumatic Encephalopathy, the trauma-caused disease that has contributed to the suicides of many professional football players.

The troubling frequency of CTE, along with the slow rate of progress that's been made on other neurological diseases led President Obama to launch the $100 million BRAIN initiative earlier this year (whether it's a good idea is another matter). The project has been compared to the Human Genome Project, with the end goal being a complete map of the brain and its "100 billion neurons making trillions of connections," as Obama put it when he announced the initiative.

Mini brains, on the other hand, might be another way to attack some of the problems neuroscientists face. They're already proving to be more useful than mouse brains at modeling some human diseases. In the Nature paper, researchers were able to model microcephaly, or "small brain" disease, a condition that often causes a sufferer to have a small head, poor brain function, and a reduced life span.

"Unlike humans, mice with [the mutation that causes the disease] show only mild brain defects or more severe defects, depending upon the mouse strain," Walsh wrote. "When [minibrains with the mutation] were cultured, cerebral organoids resembled human microcephaly—they were far smaller compared to control organoids due to premature neuronal differentiation at the expense of progenitor proliferation."

Walsh insists that scientists have little to worry about from the pro-life crowd, because the stem cells used are derived from healthy skin cells. But we're still in the infancy of this research, and when and if scientists find a way to overcome the 4 millimeter limitation, they could run into some trouble.

"Ethicists need not worry just yet, and may never need to worry, about the philosophical implications of 'consciousness in a dish,'" he wrote, because mini brains lack the complexity needed for consciousness.

But soon, he might wish he'd never mentioned it: The nascent field is advancing rapidly, so much so that mini brains "promise to advance our understanding of neuroscience and stem cell biology … and quickly."