Clearing a scientific obstacle
The success in transplanting human brain organoids into a living animal appears to remove a major barrier to using them as models of human disease. It also represents the culmination of seven years of work overseen by
Dr. Sergiu Pasca, a professor of psychiatry and behavioral sciences at Stanford.
Human brain organoids are made from
pluripotent stem cells, which can be coaxed into becoming various types of brain cells. These cells are grown in a rotating container known as a bioreactor, which allows the cells to spontaneously form brain-like spheres about the size of a small pea.
But after a few months, the lab-grown organoids stop developing, says Pasca, whose lab at Stanford devised the transplant technique. Individual neurons in the cluster remain relatively small, he says, and make relatively few connections.
"No matter how long we keep them in a dish, they still do not become as complex as human neurons would be in an actual human brain," Pasca says. That may be one reason organoids have yet to reveal much about the origins of complex neuropsychiatric disorders, he says.
So Pasca's team set out to find an environment for the organoids that would allow them to continue growing and maturing. They found one in the brains of newborn rats.
Timothy Syndrome, a very rare genetic disorder that affects brain development in ways that can cause symptoms of autism spectrum disorder.
The team compared organoids made from the stem cells of healthy people with organoids made from the stem cells of patients with the syndrome. In the lab, the cell clusters looked the same.
"But once we transplanted and we looked 250 days later, we discovered that while control cells grew dramatically, patient cells failed to do so," Pasca says.
A better model, with ethical concerns
The experiments show that Pasca's team has developed a better model for studying human brain disorders, Arlotta says.
The key seems to be providing the transplanted organoids with sensory information that they don't get growing in a dish, she says, noting that an infant's brain needs this sort of stimulation to develop normally.
"It's the stuff that we get after we are born," she says, "especially when we begin to experience the world and hear sound, see light, and so on."
But as brain organoids become more like actual human brains, scientists will have to consider the ethical and societal implications of this research, Arlotta says.
"We need to be able to watch it, consider it, discuss it and stop it if we think we think one day we are at the point where we shouldn't progress," she says. "I think we are far, far away from that point right now."
Even the most advanced brain organoids have nothing even remotely like the capabilities of a human brain, says Hyun, who posted a video
conversation he had with Pasca to coincide with the publication of the new study.
Yet many ethical discussions have focused on the possibility that an organoid could attain human-like consciousness.
"I think that's a mistake," Hyun says. "We don't exactly know what we mean by 'human-like consciousness,' and the nearer issue, the more important issue, is the well-being of the animals used in the research."
He says that wasn't a problem in the Pasca lab's experiments because the organoids didn't seem to harm the animals or change their behavior.
If human brain organoids are grown in larger, more complex animal brains, Hyun says, the cell clusters might develop in ways that cause the animals to suffer.
"What I'm concerned about," he says, "is what's next."
