Audience: High School Students
Researchers developed experiments that can image living tissues as thin as one millimeter. Photo via David Baillot/UC San Diego.
How do scientists study the brain? They obviously can’t just take it out and experiment on it, and nothing can truly mimic the capability of our brains. Humans are so unique in their own way that even animal testing wouldn’t fully cover it. However, scientists have found a way to use human tissue to mimic the brain closer than we’ve ever gotten before. These masses of human tissue are known as brain organoids: groups of neurons used in scientific study to mimic the human brain. These tiny, self-organized three-dimensional tissue cultures are derived from human stem cells. Organoids model structures that mimic regions of the brain and specific changes of neurological disorders; making them an excellent model for investigating brain development and neurological diseases.
Brain organoids aren’t literally “mini-brains”, in the sense that they can’t think or feel. They are much simpler and smaller than real brains, lacking many features that are essential for brain activity, such as blood vessels, immune cells, and connections to other organs. However, brain organoids still show some signs of neural activity, such as firing electrical signals and forming networks. Scientists can measure this activity using methods like calcium imaging (special tools to check when and where the “fuel” of the neuron is) or patch clamp analysis (which allows scientists to eavesdrop on the electrical messages that the neuron is sending and receiving). These methods can reveal how neurons communicate with each other and how they respond to different stimuli.
The development process of these organoids begins with human skin or blood cells, which scientists take and turn into induced pluripotent stem cells (iPS) — cells that can develop into any type of human cell. These iPS cells are then used to form neural stem cells, which can create most cell types found in the brain. By using different chemicals and techniques, scientists can guide neural stem cells to form brain organoids that resemble specific regions of the brain.
However, these organoids lack some of the connections and functions seen in real brains. To mimic these functions, some scientists have transplanted human brain organoids into the brains of newborn rats, where the organoids integrate with the rat tissue and mature over time. These implanted organoids can respond to stimuli and influence the rats’ behavior, offering a new way to model neurological disorders and test potential treatments. For example, after fifteen days of training, the rats learned they could get a drink from the fountain when the implanted organoid was stimulated. The human organoids were apparently sending messages to the reward-seeking regions of the rats’ brains.
Researchers at Stanford University decided to experiment with this by injecting human brain organoids into the somatosensory cortex of rat pups, a region that processes sensory information like touch or pain. They trained the rats to lick a spout for water when their human neurons were stimulated with blue light lasers. They also used a puff of air to prod the rats’ whiskers and observed how the human neurons influenced their reaction. What they found was that the human neurons were connected to the rat circuitry and became active within a second of the whisker stimulation. The human neurons also grew to six times their original size over about eight months, making up about one-third of a single hemisphere in the rat brains. The rats did not show signs of health problems like seizures or epilepsy, and most of them survived for one year after the transplants. In a way, it’s like a skin graft, except for your brain!
Unlike animal models, which have many differences from humans, brain organoids are derived from human cells and can better mimic human brain conditions. For example, scientists have used brain organoids to study autism, schizophrenia, Alzheimer's disease, and Zika virus infection. By comparing brain organoids from the stem cells of healthy and diseased individuals, scientists can identify what goes wrong in the brain and how it affects its structure and function.
On the other hand, the brain is still unmatched by modern computers. Frontier, a new supercomputer in Kentucky, is $600 million, and takes up 6,800 square feet. Last year, for the first time, this computer achieved the computational capacity of a single human brain, but using a million times more energy. Scientists have started to find ways to merge these tissues with technology to make processing more efficient– these devices are known as biocomputers. It could take years, maybe even decades before organoids can power systems as small as a computer mouse; but by scaling up organoid production training them with AI, these biocomputers could support superior computing speed, processing power, data efficiency, and storage capabilities.
Bibliography:
Candanosa, Roberto Molar. “Could Future Computers Run on Human Brain Cells?” The Hub, 28 Feb. 2023, https://hub.jhu.edu/2023/02/28/organoid-intelligence-biocomputers/. Accessed 31 Jan. 2024.
Dunlap, Tiare. “Making Lab-Grown Brain Organoids ‘Brainier.’” UCLA, UCLA, 29 Sept. 2022, newsroom.ucla.edu/releases/making-mini-brain-organoids-brainier.
Fischbach, Mark, host. “New Year, New Brain.” Distractible, narrated by Wade Barnes and Bob Muyskens, Wood Elf, 31 Dec. 2023, open.spotify.com/show/2X40qLyoj1wQ2qE5FVpA7x.
Goldman, Bruce. “Human Brain Cells Transplanted into Rat Brains Hold Promise for Neuropsychiatric Research.” News Center, https://med.stanford.edu/news/all-news/2022/10/human-rat-brain-neuron.html. Accessed 14 Jan. 2024.
Shou, Y., Liang, F., Xu, S., & Li, X. (n.d.). The application of brain organoids: From neuronal development to neurological diseases. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.579659
Zimmer, Carl. “Human Brain Cells Grow in Rats, and Feel What the Rats Feel.” The New York Times, 12 Oct. 2022, https://www.nytimes.com/2022/10/12/science/human-brain-cells-organoids-rats.html. Accessed 14 Jan. 2024.
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