Stanford researchers create mice with human brain cells, raising ethical questions

The team used genetic tools to breed mice missing most cells of the cortex and hippocampus, according to MIT Technology Review. NPR reported that the mice were missing most of their cerebral cortexes. Pașca said the altered animals had space for human cells, which divide, grow, and within weeks to months take most of that space. NPR reported that earlier attempts were limited because human brain cells develop at least 20 times slower than mouse cells. In normally developing mice, neurons formed rapid networks and outcompeted human cells. By removing parts of the mouse nervous system precisely, Pașca said, the team gave human cells more opportunity to connect.

The mice without added human cells were still fairly functional, according to MIT Technology Review. They walked around and squeaked, but they had memory problems. In a maze test, they could not remember what parts they had explored. Mice with the added human cells performed better on the maze test, suggesting the human tissue played some role in the animals’ cognition. NPR reported that the mice with human brain cells were also better at memory tasks and interacting with other mice. Pașca said many deficits present in the depleted mice were no longer present, suggesting human cortical cells might help restore some lost functions.

The modified mice also showed differences relevant to disease. NPR reported that mice with human brain cells had trouble walking properly after their brains were deprived of oxygen, while ordinary mice are resilient to low-oxygen conditions. Pașca said this more human-like reaction could make the animals better models for brain conditions linked to low oxygen, such as cerebral palsy, intellectual disability, and epileptic encephalopathies. He said the approach could be powerful for tackling questions of disease and developing therapeutics.

MIT Technology Review reported that brain organoids are already being tested in labs to see if they can be connected to computers to play video games, and other scientists have proposed using them like replacement parts to treat stroke victims. Carsten Charlesworth, a scientist in a different Stanford lab who was not involved in the research, said the report demonstrated the combined power of genetic engineering and stem-cell technology to reshape biology. He said what was most remarkable was the extent to which human neural tissue introduced after birth grew and connected with the mouse nervous system across a species barrier. He added that as these technologies advance, they will increasingly force people to challenge traditional assumptions.

Ethical questions remain. MIT Technology Review reported that Pașca convened a group of ethics experts last year to study the implications of neural organoid technology, including the odds that an animal could develop human consciousness and the risk that organoid therapy clinics might offer scam treatments to desperate patients. NPR reported that Pașca said the research was conducted with strong ethical oversight. Pașca said he is not now concerned that the rodents have any type of human cognitive capacities, because their brains are relatively tiny and the evolutionary distance between humans and mice is great. But he cautioned against adding human brain organoids to higher species. He called doing the experiment in a primate a very clear red line and said he does not think it is justified at this point.

Outside researchers praised the work while pointing to future questions. NPR reported that Hongkui Zeng, executive vice president and director of brain science at the Allen Institute in Seattle, who was not affiliated with the study, described it as a powerful technology to study human neurons and how human brain circuits can form in a more natural environment than a petri dish. She added that going forward there will be considerations, if not concerns, such as the implications of deploying the technique in larger and longer-living animals.