Quirks and Quarks

We're making tiny brains in the lab — should we be worried for them?

Brain waves were detected in lab-grown brain organoids this summer. Could they become complex enough to think?

Could brain organoids one day become complex enough to be self-aware?

Dr. Alysson Muotri holding a 6-well dish with 3-D brain organoids floating in a redish medium. Each white small sphere inside the wells is one brain organoid. (Erik Jepsen/UCSD)

The announcement this summer that researchers had detected brain waves in "mini-brains" they'd grown in the lab has raised a whole new set of important ethical questions around this kind of fundamental research.

Brain organoids have emerged in recent years as a powerful new biomedical tool to study human brain development and disorders of the brain like Alzheimer's and multiple sclerosis. 

But as researchers develop techniques to grow these nodules of brain tissue ever larger and with more neurological complexity, the work is raising profound ethical questions about whether they might one day be able to think and feel pain. 

"If we really are capable of producing something similar to the human brain, then this will open a can of ethical worms that will distinguish [brain organoid] research from other areas of biomedical inquiry," Canadian bioethicist Kalina Kamenova told Quirks & Quarks host Bob McDonald. 

Brain organoids can be a test bed for new therapies

For the last decade, researchers have been using stem cells to grow clusters of neurons and glial cells — the critical cell types that make up the brain — in bio-reactors that provide carefully tailored conditions for growth. As the cells multiply, they're able to self-organize to resemble a fragment brain tissue similar to a piece of a developing brain. 

Oligocortical organoids grown in a culture from Dr. Paul Tesar's lab (Mayur Madhavan)

"Brain organoids provide us an opportunity to study how the human brain develops and functions, and provide us key insights into neurological disorders that we simply could not study before," said Paul Tesar, from the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Tesar has been using human brain organoids to test new treatments for multiple sclerosis.  MS is characterized by the loss of myelin — an insulating sheath around nerve cells. In previous work, Tesar and his colleagues had developed a drug that proved effective in stimulating brain tissue to regenerate myelin which they had tested in mice. 

Using human brain organoids, the team was able to show the drug was also effective in human brain tissue, and they're now moving towards clinical trials in MS patients.

The beginning of a thinking, feeling brain 

Work on brain organoids took a new turn when prominent neuroscientist Alysson Muotri from the University of California at San Diego, published a paper in August that reported on the detection of brain waves in brain organoids for the first time. 

Muotri is a scientist known for pushing boundaries in research, having previously studied the effects of space travel on brain organoids and developed brain organoids from stem cells modified with Neanderthal genes.

A cross section of a brain organoid showing how the brain cells self-assemble into structures that resemble the human developing brain (Muotri Lab/UCSD)

Prior to the publication of Muotri's most recent work, many organoid researcher had been skeptical that brain organoids would ever generate brain waves. Outside of a body, many thought the conditions weren't right for brain organoids to mature and form the neural circuits necessary for coordinated electrical activity.

Muotri's lab was able to optimize their growth formula so they could grow organoids that could live for several years.

Initially, they observed no coordinated activity, just occasional random firing of neurons. However, as the brain organoids started to mature, they began to observe increasing synchronization of activity as the neurons formed synapses over time. Eventually, this developed into waves of neural electrical activity that were similar to brainwaves observed in preterm infants. 

Muotri thinks his experiments have demonstrated that brain organoids are capable of forming the sophisticated networks that are associated with human behaviour and cognition.

"What we see in the brain organoid is the beginning of something that will lead to these sophisticated networks," said Muotri. "That's why this is so important."

'I want to create the entire human brain in vitro'

Muotri is so convinced of the value of brain organoids in studying human brain disorders that he wants to continue to push the field forward, and face the ethical hurdles as they come.

Even the most advanced organoid models today are far from a fully functioning brain. They don't represent all the cell types in the brain, let alone the differentiation of different brain regions.

Dr. Alysson Muotri working in his lab (Erik Jepsen/UCSD)

But Muotri is pushing for that development, and thinks it's entirely possible to do so. His lab has already grown organoids similar to cortical tissue and is working on a mini-thalamus. He's looking towards interconnecting these, perhaps providing sensory information to the brain organoids to help them 'see.' 

"As we do that, what we expect to happen is the maturation of these organoids to increase and to become closer to the adult brain."

Could this mean brain organoids could one day feel other sensations, like pain or even at some point become self-aware. Muotri admits it's possible. 

"We're getting closer and closer to a more grey zone," he admits. But he thinks the protocols we've already established for working humanely with animals and human subjects can help us understand the limits.

"That's when we team up with the ethicists to really decide how to use this material, and how to treat these brain organoids."

Canadian bioethicist Kalina Kamenova advises caution to be taken with the field going forward, and advocates for ethical oversight to monitor the research and to establish boundaries. 

"[At some point], we'll need to establish whether we're dealing with human beings here and what moral standing it has, and what kind of legal protection should be afforded to it." 

Muotri agrees that the field will need to be regulated in the future so as to ensure we treat brain organoids ethically — perhaps mandating how to discard them after use and how many organoids to grow for each experiment. But he cautions against putting the brakes on the research too soon. 

"I think the first thing we need to do is to see if we can actually get to that stage where these organoids are self-aware or if they feel pain," said Muotri. "I think, right now, it's premature and might actually damage the research. If we do actually get to that level, then I think it's time to pause and think about the consequences, and discuss with everybody in the field how far is too far and where is the limit."