When a fetus reaches six months old, it starts to produce electrical signals resembling brain waves. Now, we know that clusters of lab-grown human brain cells, known as organoids, follow a similar developmental timeline, according to a recent paper in the journal Cell Stem Cell. This suggests that organoids can help scientists understand early phases of brain development and shines light onto conditions such as autism and schizophrenia.
"After these organoids are in that six-to-nine-months range, that's when [the electrical patterns] start to look a lot like what you'd see with a preterm infant," says Dr. Alysson Muotri, director of the stem cell program at the University of California, San Diego.
Human brain tissue grown in a dish may offer insights into brain conditions, such as autism and schizophrenia.
Photo credit: NPR, Alysson Muotri/UC San Diego Health Sciences
In the study, Muotri and colleagues at the University of California, San Diego altered human skin stem cells and coaxed them to develop as human brain cells do in an embryo. These tiny organoids contained a variety of cell types that produce the same chemicals and electrical signals as mature brain cells. The team used multielectrode arrays to monitor neural activity and after two months they detected bursts of brain waves. The signals were sparse but had a frequency pattern similar to immature human brain cells. As the organoids continued to grow, researchers measured brain waves at different frequencies, and in more regular patterns, which is characteristic of sophisticated neural networks.
To compare organoid brain wave patterns with those of human brains, the team trained a machine-learning algorithm with brain wave recordings from 39 premature babies between six and nine-and-a-half months old. Interestingly, the algorithm accurately predicted how many weeks the organoids had developed, verifying that the organoids showed a similar growth trajectory to that of the human brain.
These results support the idea that organoids offer a way to study a wide range of brain abnormalities, especially those that cannot be replicated in animal models. "You can use brain organoids for several things, including understanding normal human neurodevelopment, disease modeling, brain evolution, drug screening, and even to inform artificial intelligence," Muotri says.
But ethicists say that this research needs guidelines; especially when considering whether or not these ‘mini brains’ can one day become conscious. It is possible that these organoids can eventually develop sentence-like capabilities, or maybe even perceptions of pain.
"If we're starting to see spontaneous brain activity that grows and develops as the organoid grows and develops, then we need to have some concerns about how ought we regard these things," says Nita Farahany, professor of law and philosophy at Duke University. "Do they have some moral status?"
The National Institutes of Health recognizes the problem and are developing guidelines for researchers, says Farahany, who sits on the NIH Neuroethics Working Group.