In Paola Arlotta’s lab at Harvard University in the US is a long, windowless hallway that is visited every day by one of her scientists. They go there to inspect racks of scientific muffin pans. In every cavity of every pan is a pool of pink liquid, at the bottom of which are dozens of translucent nuggets no bigger than peppercorns.
The nuggets are clusters of neurons and other cells, as many as 2 million, normally found in the human brain. On their daily rounds, the scientists check that the nuggets are healthy and well-fed.
The oldest nuggets are now seven years old. Back in 2018, Arlotta and her colleagues created them from skin cells originally donated by volunteers. A chemical cocktail transformed them into the progenitor cells normally found in the foetal human brain.
The cells multiplied into neurons and other types of brain cells. They wrapped their branches around each other and pulsed with electrical activity. One such nugget can contain more neurons than the entire brain of a honeybee. But Arlotta is quick to stress that they are not brains. She and her colleagues call them brain organoids.
After the organoids started growing in 2018, their neurons began behaving like those in a foetal human brain, down to the way their genes switched on and off. And as the months passed, the neurons matured to resemble the neurons in a baby after birth.
As months turned to years, Arlotta’s team set a record for the oldest documented brain organoids.
Arlotta finds the progress exciting. “It’s a whole new branch of science that was not there before,” she said. But last month, Arlotta and 16 other scientists called for worldwide oversight of brain organoid research, to ensure that the field remains on safe ethical ground.
But that oversight needs to be based on what brain organoids actually are, rather than what we might fear or hope for them, said Dr Sergiu Pasca, a neuroscientist at Stanford University, US, and an author of the commentary. Talking about the ethics of brain organoids is still important, he added. A fortnight ago, Dr Pasca hosted a meeting of scientists, philosophers and others in Pacific Grove, California, to discuss these issues.
Insoo Hyun, a bioethicist at the Hastings Center for Bioethics, US, and another author of the commentary, was there. He shared his concerns about how large-scale arrays of organoids created for computers might spontaneously gain some features of the human brain.
Such philosophical questions felt remote a decade ago when the first brain organoids started growing. At the time, scientists were mostly surprised that the experiments worked at all.
As word of that research spread, other scientists started teaching themselves how to grow brain organoids. That progress allowed for large-scale experiments that would have been impossible to run on actual human brains. The experiments, in turn, have enabled scientists to eavesdrop on the chemical conversation that leads brain cells to develop into different kinds of neurons. Scientists have also observed cells migrating within organoids and joining together into the networks that let our brains process information.
Some scientists are using brain organoids to find clues to how autism and other conditions arise during pregnancy. Lilia Iakoucheva, a neuroscientist at the University of California, San Diego, US, and her colleagues have grown brain organoids from skin cells donated by children with autism. The neurons in their organoids wander off course, the researchers found.
“If neurons do not migrate to the proper places, you can imagine that can actually damage a foetal brain and cause the symptoms that we are seeing after birth,” Iakoucheva said.
Dr Pasca and his colleagues found that another form of autism, caused by a condition known as Timothy syndrome, leads some neurons to wire incorrectly to others. Other disorders come about when entire circuits connecting different regions of the brain become disrupted. To study them, scientists are joining organoids into tiny networks known as assembloids.
In April, Dr Pasca and his colleagues published details about an assembloid they created to study how pain signals travel from our skin to our brains. They created organoids for the four regions of the nervous system that make up the pain pathway.
The researchers exposed the sensory neurons to the molecule that makes chillies hot. The sensory organoid generated signals, which travelled along the chain of other organoids; the neurons across the four regions even fired in synchrony.
Dr Pasca and his colleagues then grew the assembloids with a mutation known to make people highly sensitive to pain. The mutation made the synchrony even stronger.
When Feng Guo, a biomedical engineer at Indiana University, US, first learnt about brain organoids seven years ago, he wondered if he could use them to do more than understand the development of human brains. Maybe he could watch them process information.
To find out, he and his colleagues built Brainoware, a system for studying organoids. They created wiring that could deliver electrical signals to organoids, and then built devices that could eavesdrop on the electrical activity organoids made in response. Guo is collaborating with Hyun, the bioethicist, to consider what might happen if systems like Brainoware live up to his hopes.
One possibility is that brain organoids could become conscious — not the full-blown consciousness we experience with 86 billion intricately wired neurons but a simpler version.
Last year, hundreds of scientists signed a declaration stating that there was “a realistic possibility of conscious experience” in many animals, including honeybees. If that’s the case for honeybees, would it be true for organoid-based computers with more neurons? Some bioethicists have been exploring that possibility.
NYTNS