On October 12, 2022, a Melbourne led group demonstrates 800,000 human brain cells living in a dish can play pong —DishBrain— and perform goal-directed activities after responding to pulses of electricity
- Live biological neurons show more about how a brain works than AI ever will
The results of the study are published today in the journal Neuron and have attracted global attention overnight.
Dr Brett Kagan, who is Chief Scientific Officer of biotech start-up Cortical Labs says we have shown we can interact with living biological neurons in such a way that compels them to modify their activity, leading to something that resembles intelligence.
The co-authors are affiliated with Monash University, RMIT University, University College London and the Canadian Institute for Advanced Research.
Dr Hon Weng Chong, Chief Executive Officer of Cortical Labs says DishBrain offers a simpler approach to test how the brain works and gain insights into debilitating conditions such as epilepsy and dementia
Scientists have for some time been able to mount neurons on multi-electrode arrays and read their activity, but this is the first time that cells have been stimulated in a structured and meaningful way.
“In the past, models of the brain have been developed according to how computer scientists think the brain might work,” Kagan says. “That is usually based on our current understanding of information technology, such as silicon computing.
“But in truth we don’t really understand how the brain works.”
By building a living model brain from basic structures in this way, scientists will be able to experiment using real brain function rather than flawed analogous models like a computer.
Kagan and his team, for example, will next experiment to see what effect alcohol has when introduced to DishBrain.
“We’re trying to create a dose response curve with ethanol – basically get them ‘drunk’ and see if they play the game more poorly, just as when people drink,” says Kagan.
That potentially opens the door for completely new ways of understanding what is happening with the brain.
Dr Adeel Razi, Director of Monash University’s Computational & Systems Neuroscience Laboratory says this new capacity to teach cell cultures to perform a task in which they exhibit sentience.
“By controlling the paddle to return the ball via sensing – opens up new discovery possibilities which will have far-reaching consequences for technology, health, and society,”
“We know our brains have the evolutionary advantage of being tuned over hundreds of millions of years for survival. Now, it seems we have in our grasp where we can harness this incredibly powerful and cheap biological intelligence.” says Dr Adeel Razi
The findings also raise the possibility of creating an alternative to animal testing when investigating how new drugs or gene therapies respond in these dynamic environments.
“We have also shown we can modify the stimulation based on how the cells change their behavior and do that in a closed-loop in real time,” Kagan added
Researchers used microelectrode arrays to both stimulate and detect mouse brain cells from embryonic brains and human brain cells derived from stem cells, to conduct the study.
Using one array, Dishbrain determined whether the ball was on the left or right by firing electrodes.
The paddle provided distance information by sending frequent signals.
Feedback from the electrodes taught DishBrain how to return the ball, by making the cells act as if they themselves were the paddle.
DishBrain learned how to return the ball by making the cells act as if they were the paddle, based on feedback from the electrodes.
“We’ve never before been able to see how the cells act in a virtual environment,” says Kagan.
“We managed to build a closed-loop environment that can read what’s happening in the cells, stimulate them with meaningful information and then change the cells in an interactive way so they can actually alter each other.”
“The beautiful and pioneering aspect of this work rests on equipping the neurons with sensations — the feedback — and crucially the ability to act on their world,” says co-author Professor Karl Friston, a theoretical neuroscientist at UCL, London.
“Remarkably, the cultures learned how to make their world more predictable by acting upon it. This is remarkable because you cannot teach this kind of self-organisation; simply because — unlike a pet — these mini brains have no sense of reward and punishment,” he says.
“The translational potential of this work is truly exciting: it means we don’t have to worry about creating ‘digital twins’ to test therapeutic interventions.”
“We now have, in principle, the ultimate biomimetic ‘sandbox’ in which to test the effects of drugs and genetic variants – a sandbox constituted by exactly the same computing (neuronal) elements found in your brain and mine.”
The research also supports the “free energy principle” developed by Professor Friston.
“We faced a challenge when we were working out how to instruct the cells to go down a certain path. We don’t have direct access to dopamine systems or anything else we could use to provide specific real-time incentives so we had to go a level deeper to what Professor Friston works with: information entropy – a fundamental level of information about how the system might self-organise to interact with its environment at the physical level.
“The free energy principle proposes that cells at this level try to minimise the unpredictability in their environment.”
Kagan says one exciting finding was that DishBrain did not behave like silicon-based systems. “When we presented structured information to disembodied neurons.
“We saw they changed their activity in a way that is very consistent with them actually behaving as a dynamic system,” says Kagan
“For example, the neurons’ ability to change and adapt their activity as a result of experience increases over time, consistent with what we see with the cells’ learning rate.”
Chong says he was excited by the discovery, but it was just the beginning.
“As one of our collaborators said, it’s not every day that you wake up and you can create a new field of science.” says Kagan
Repairing injuries to human brains.
Dr. Isaac Chen, a neurosurgeon and organoid researcher at the University of Pennsylvania who was not involved in the research, saw another possibility in the new study: the repair of injuries to human brains.
Dr. Chen envisioned growing brain organoids from the skin of a patient with a damaged cortex. Once injected into the brain of the patient, the organoid might grow and wire up with healthy neurons.
“This idea is definitely out there,” he said. “It’s just a matter of, How do we take advantage of it, and take it to the next level?”
Watch human brain cells in a dish learn to play Pong in real time
“This is brand new, virgin territory. And we want more people to come on board and collaborate with this, to use the system that we’ve built to further explore this new area of science,” says Kagan
