Research on conditions like autism, schizophrenia and even brain cancer increasingly relies on clusters of human cells called brain organoids.
These pea-size bits of neural tissue model aspects of human brain development as they grow for months and even years in a lab. They also make many people uneasy, in part because the brain is so closely tied to our sense of self.
A group of scientists, ethicists, patient advocates and journalists met for two days in Northern California this fall to discuss how scientists, and society, should proceed.
Among the questions:
- Is it okay to place human organoids in an animal's brain?
- Can organoids feel pain?
- Can they become conscious?
- Who, if anyone, should regulate this research?
"We are talking about an organ that is at the seat of human consciousness. It's the seat of personality and who we are," says Insoo Hyun, a bioethicist at the Museum of Science, Boston, who attended the meeting.
"So it's reasonable to be especially careful with the kind of experiments we're doing," he says.
Societal issues by the sea
The event was hosted by Dr. Sergiu Pașca, a prominent organoid researcher whose lab at Stanford University used the technology to develop a potential treatment for a rare cause of autism and epilepsy.
Organoids are allowing scientists to study brain cells and circuits that don't exist in animals, Pașca says.
"For the first time, we have this ability to really work with human neurons and human glial cells," he says, "and ask questions about these really mysterious disorders of the brain."
But Pașca's work has sometimes caused public unease as his lab has recreated a human pain pathway, and transplanted a human organoid into the brain of a rat.
"Of course, there are issues of ethics and societal implications and religious views that have to be taken into consideration," he says. Many of those issues were outlined in a recent article by Pasca and others in the journal Science.
To take the next step, Pașca invited a group to the Asilomar Conference Center on the Monterey Peninsula. It's the spot where, 50 years earlier, another group met to hash out the first ethical guidelines for genetic engineering.
Organizers of the organoid event had more modest expectations.
"Our goal for this meeting was to just bring everybody together across all these fields and start brainstorming," Pașca says.
That happened — in formal sessions, coffee breaks, after-hours social gatherings and even walks on the beach. And participants brought widely varying perspectives.
Risk vs. reward
Scientists and patient advocates at the meeting often emphasized the need to quickly answer questions and find cures.
Bioethicists were more likely to speak about the importance of guardrails to make sure people consent to having their cells made into organoids, and to discourage any efforts to enhance the brains of animals or humans.
There was consensus, though, on the need to keep the public informed.
When people hear about brain organoid research, they tend to have one overarching and quite reasonable question for scientists, says Alta Charo, professor emerita of law and bioethics at the University of Wisconsin, Madison.
"How far along are they in building organoids that can actually recapitulate something that we associate with human capacities?" she says. "Have we reached a point where we're worried?"
Not yet, probably. But the prospect seems closer now that scientists are linking multiple organoids to create more brain-like structures called assembloids, Charo says.
Pasca's team, for example, has built a network of four organoids to model the pathway that carries pain signals to the brain.
That sounds disturbing, Charo says, unless you understand that this network of cells lacks the circuitry to feel pain.
"The mere existence of the pain pathway, I think, is enough to give a public perception problem that the organoid or the assembloid is suffering," Charo says. "And yet, if the pathway that allows for this emotional aversion doesn't exist, then there's no suffering."
And no ethical issue, for now.
Even so, she says, researchers and regulators should probably be looking ahead, rather than waiting until there is an actual problem.
A perception problem
Several participants faulted the media for glossing over the current limits on what organoids can do, and for describing these clusters of cells as "mini-brains."
That sort of coverage has led some people to falsely believe there are labs with "brains growing in a petri dish," says Dr. Guo-li Ming, an organoid researcher at the University of Pennsylvania.
Scientists need to counter that notion and explain how organoid research is helping people with life-threatening diseases, Ming says.
Her own lab, for example, is working to customize brain cancer treatment using organoids derived from a patient's own tumor cells. That allows doctors to ensure a cancer drug is effective for the patient's specific tumor.
Ming also thinks it's too soon to worry about organoids becoming conscious because "we're far from mimicking the brain activity in real human beings."
Even so, organoid scientists "definitely need some guidelines," Ming says, because of current public concern and the potential for inappropriate research in the future.
New cells, old issues
The ethical and societal issues surrounding brain organoids echo those related to stem cell research more than 20 years ago.
Back then, there was concern that neural stem cells might give animals human-like cognitive abilities.
It turned out those human cells didn't do well in another species' brain. But organoids, which start out as stem cells, can thrive in animal brains and even integrate with their circuitry.
"So what used to be a very hot issue in stem cell research has now come back," Hyun says.
Hyun was part of a group that worked on organoid guidelines for the International Society for Stem Cell Research five years ago, when the need for oversight seemed less pressing.
"We had a let's wait and see attitude," he says, because it was not clear how long it would take for organoid technology to become concerning. "We've gotten to the point rather quickly."
Hyun's immediate concern is protecting research animals from organoid experiments that could cause suffering. But in the long term, he says, it may take guidelines and government oversight to ensure that organoid research doesn't harm, or horrify, people.
The Asilomar meeting suggests many scientists know that, and want help navigating this new scientific frontier.
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