Scientists Create Mice With Brains That Are Partly Human

Scientists have bioengineered mice whose brains contain working human cells, but they stress that they're not "mice that think like humans." In a study published in Nature, Stanford University neuroscientists say they engineered mice to have almost no cerebral cortex of their own, leaving around half the volume of their brains missing. They then implanted clusters of lab-grown human brain tissue, known as organoids. Those cells grew and wired themselves into the animals' existing brain circuits and spinal cord, forming connections visible on scans. The hope is to create better models for complex disorders such as autism, epilepsy, and cerebral palsy—conditions that don't naturally appear in rodents and for which current treatments are often ineffective, the BBC reports.

The researchers say the breakthrough could be "transformative" for some conditions. "Here we have a new model that allows us to actually capture aspects of human brain function in a way that has not been possible before," says lead researcher Sergiu Pasca. "We can derive cells from patients with frontotemporal dementia or other neurological conditions, transfer them into these mice, test the animals for cellular or circuit-level correlates of behavioral disability, and then screen therapeutic candidates."

• Researchers were surprised to discover that mice missing most of their cerebral cortex functioned relatively normally, though they had a more cautious gait and tended to be forgetful, the Telegraph reports. Three months after the organoids were implanted, over 90% of their cortical tissue was human. After six months, they behaved much like ordinary mice during standard tests, with no "enhancement" detected, researchers say.

• Researchers were also surprised to see that some of the human brain cells in the mice developed into giant cells known as von Economo neurons. They are only found in "large, social animals" like whales and humans, the New York Times reports. They are the first cells to decline in frontotemporal dementia, and scientists have been unable to grow them in labs. "We're trying to see whether mutations that are associated with frontotemporal dementia are making the cells uniquely susceptible to disease," Pasca says. "And why? Why is this happening?
• Ethicists and outside scientists call the work both impressive and fraught. They say the research raises questions about how altered cognition in lab animals should be understood and regulated. The animals, researchers say, are bred and handled under strict welfare rules, and the specialized mice are expected to be used only in a small number of labs focused on specific brain disorders.
• Hongkui Zheng, director of brain science at the Allen Institute in Seattle, tells the Times that he's concerned about what could happen if human cells were placed in the brains of animals like pigs, where they would have much more room to grow. He says there's a need for "ethical oversight and regulation," a move Pasca and other scientists called for in a report issued earlier this month.