Brain organoids are helping researchers, but raise ethical questions : Shots

Cross section of a two-month-old brain organoid observed under a fluorescence microscope.

Pasteur Institute-SupBiotech/NASA

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Pasteur Institute-SupBiotech/NASA

Research into diseases like autism, schizophrenia and even brain cancer increasingly relies on clusters of human cells called brain organoids.

These pea-sized pieces of neural tissue model aspects of human brain development as they grow over months, or even years, in a laboratory. They also worry many people, in part because the brain is so closely linked 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 OK 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’re talking about an organ that is 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 in Boston, who attended the meeting.

“It is therefore reasonable to be particularly careful with the type of experiments we conduct,” he says.

Societal issues by the sea

The event was hosted by Dr. Sergiu Pașca, a leading organoid researcher whose Stanford University laboratory has used this technology to develop a potential treatment for a rare cause of autism and epilepsy.

Organoids allow scientists to study brain cells and circuits that do not exist in animals, said Pasca.

“For the first time, we have this ability to actually 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 sparked public unease because his lab has recreated the human pain pathway and transplanted a human organoid into a rat’s brain.

“Of course, there are questions of ethics, societal implications and religious views that need to be taken into consideration,” he says. Many of these issues were highlighted 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. This is the place where, 50 years earlier, another group met to develop the first ethical guidelines for genetic engineering.

Organizers of the organoid event had more modest expectations.

“Our goal for this meeting was just to bring everyone together in all these areas and start brainstorming,” says Pașca.

This happened during formal sessions, coffee breaks, after-hours social gatherings, and even walks on the beach. And the participants brought very varied points of view.

Risk vs Reward

Scientists and patient advocates at the meeting often stressed the need to quickly answer questions and find cures.

Bioethicists were more likely to talk about the importance of guardrails to ensure that people consent to having their cells transformed into organoids and to discourage any efforts to improve the brains of animals or humans.

There is, however, consensus on the need to keep the public informed.

When people hear about brain organoid research, they tend to ask a very reasonable and overarching question of scientists, says Alta Charo, professor emeritus of law and bioethics at the University of Wisconsin at Madison.

“Where are they in building organoids that can recapitulate something we associate with human capabilities?” she said. “Have we reached a point where we’re worried?”

Not yet, probably. But the prospect seems closer now that scientists are connecting multiple organoids to create more brain-like structures, called assembloids, Charo says.

Pasca’s team, for example, built a network of four organoids to model the pathway that transmits pain signals to the brain.

That sounds worrying, Charo says, unless you understand that this network of cells doesn’t have the circuitry needed to feel pain.

“The mere existence of the pain pathway, I think, is enough to give the public a perception problem that the organoid or assemblyoid is in pain,” says Charo. “And yet, if the pathway that allows for this emotional aversion does not exist, then there is no suffering.”

And no ethical problem, for the moment.

Still, she says, researchers and regulators should probably look to the future, rather than waiting until there’s a real problem.

A problem of perception

Several participants criticized the media for ignoring the current limits of what organoids can do and describing these clusters of cells as “mini-brains.”

This kind of media coverage has led some people to falsely believe that 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 this idea and explain how organoid research helps people with life-threatening illnesses, Ming says.

His own lab, for example, is working to personalize brain cancer treatment using organoids derived from a patient’s tumor cells. This allows doctors to ensure that an anticancer drug is effective for the patient’s specific tumor.

Ming also thinks it’s too early to worry about organoid awareness, because “we are far from mimicking the brain activity of real human beings.”

Even so, organoid scientists “definitely need guidelines,” Ming says, because of current public concerns and the risk of inappropriate research in the future.

New cells, old problems

The ethical and societal issues surrounding brain organoids echo those related to stem cell research more than 20 years ago.

At the time, there was concern that neural stem cells could give animals human-like cognitive abilities.

It turned out that these human cells did not work well in the brains of another species. But organoids, which are the origins of stem cells, can thrive in animal brains and even integrate into their circuits.

“What was once a very hot topic in stem cell research has now re-emerged,” says Hyun.

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 surveillance seemed less pressing.

“We took a wait-and-see attitude,” he says, because it was unclear how long it would take for organoid technology to become a concern. “We got to the point pretty quickly.”

Hyun’s immediate concern is protecting laboratory animals from organoid experiments that could cause suffering. But in the long run, he says, there may need to be guidelines and government oversight to ensure that organoid research doesn’t harm or horrify people.

The Asilomar meeting suggests that many scientists know this and want help in crossing this new scientific frontier.