The story so far:
Scientists at Johns Hopkins University (JHU) recently outlined a plan for a potentially revolutionary new area of research called “organoid intelligence”, which aims to create “bio-computers”. Here, brain cultures grown in the lab are coupled to real-world sensors and input/output devices. The scientists expect the technology to harness the processing power of the brain and understand the biological basis of human cognition, learning, and various neurological disorders.
What is the premise of this tech?
Understanding how the human brain works has been a difficult challenge. Traditionally, researchers have used rat brains to investigate various human neurological disorders. Now, in a quest to develop systems that are more relevant to humans, scientists are building 3D cultures of brain tissue in the lab, called brain organoids. These “mini-brains” (with a size of up to 4 mm) are built using human stem cells and capture many structural and functional features of a developing human brain. However, the human brain also requires various sensory inputs (touch, smell, vision, etc) to develop into the complex organ it is, and brain organoids developed in the lab aren’t sophisticated enough. They also do not have blood circulation, which limits how they can grow.
Then, how do we study the brain?
Recently, scientists transplanted these human brain organoid cultures into rat brains, where they formed connections with the rat brain, which in turn provided circulating blood. Since the organoids had been transplanted to the visual system, when the scientists showed the experimental rats a light flash, the human neurons were activated, too, indicating that the human brain organoids were also functionally active. Scientists have touted such a system as a way to study brain diseases in a human context. However, human brain organoids are still nested in the rat-brain microenvironment. The effects of drugs in this model will have to be interpreted through various behavioural tests in rats, which could be insufficiently representative. Therefore, we need to address the limitations of lab-grown organoids and develop a more human-relevant system.
What is the new ‘bio-computer’?
The JHU researchers’ scheme will combine brain organoids with modern computing methods to create “bio-computers”. They have announced plans to couple the organoids with machine learning by growing the organoids inside flexible structures affixed with multiple electrodes (similar to the ones used to take EEG readings from the brain). These structures will be able to record the firing patterns of the neurons and also deliver electrical stimuli, to mimic sensory stimuli. The response pattern of the neurons and their effect on human behaviour or biology will then be analysed by machine-learning techniques. Recently, scientists were able to grow human neurons on top of a microelectrode array that could both record and stimulate these neurons. Brain organoids can also be developed using stem cells from individuals with neurodegenerative or cognitive disorders. Comparing the data on brain structure, connections, and signalling between ‘healthy’ and ‘patient-derived’ organoids can reveal the biological basis of human cognition, learning, and memory.
Are ‘bio-computers’ ready for commercial use?
Currently, brain organoids have a diameter of less than 1 mm and have fewer than 1,00,000 cells (both on average), which make it roughly three-millionth the size of an actual human brain. So scaling up the brain organoid is key to improving its computing capacity. Thomas Hartung, a professor of evidence-based toxicology at JHU who is leading this work, said that “the challenge is now to establish long-term memory. We hope to achieve this within 1-2 years. Applying this to patient cell-derived brain organoids, like autism and Alzheimer donors, is already on the way. We might see benefits for drug development in this decade.”
Surat Parvatam is senior research associate at the Atal Incubation Centre–Centre for Cellular and Molecular Biology, Hyderabad.
