Tiny lab-grown 'brains' can gain consciousness and feel pain—and we're not ready for that.

Some scientists claim that miniature brain models grown in labs could soon achieve consciousness. However, our current regulations don't allow for this. (Image courtesy of Francesco Carta fotografo via Getty Images)

Scientists are getting closer to growing human brains in the lab, sparking ethical debates about the welfare of these lab-grown tissues.

Controversy surrounds “brain organoids,” sometimes mistaken for the “brains in boxes” of science fiction. However, these small structures of brain tissue, grown from stem cells, are too simple to function like a real human brain. Consequently, scientists have suggested that brain organoids lack consciousness, leading to lax research regulations.

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“We believe the pendulum has swung too far in the opposite direction due to fear of science fiction-inspired hype and exaggeration,” Christopher Wood, a bioethics researcher at Zhejiang University in China, told Live Science in an email. In a review article published September 12 in the journal Patterns, Wood and his colleagues argue that technological advances could soon lead to the creation of conscious organoids.

The authors argue that the rules governing the use of organoids should be reconsidered. According to Boyd Lomax, a neurobiologist at Johns Hopkins University, it would be unethical for a conscious organoid to have its own thoughts and interests, or to feel pain.

However, taming the mind may not be so easy.

Consciousness is difficult to define.

Stem cells used to create brain organoids grow side by side and exhibit a simple organization when cultured on a two-dimensional surface, such as a Petri dish. However, when grown in a solid gel or a rotating bioreactor that suspends the cells in mid-air, they develop three-dimensional anatomical networks reminiscent of those observed in the embryonic brain.

Despite the fact that brain organoids acquire three-dimensional features, some neuroscientists argue that they are too simple to possess consciousness. Consciousness in the real brain arises from the interaction of its various regions, but organoids resemble only one part. And none of these lab-grown mini-brains exceeds 4 millimeters in diameter, suggesting the absence of functions essential for consciousness.

People often think of consciousness in humans and animals as a state of self-awareness. However, “we view consciousness in organelles as a basic level of sensation, the ability to experience pain and pleasure,” says Andrea Lavazza, a moral philosopher and neuroethicist at Pegaso University in Italy.

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Most neuroscientists define consciousness as self-awareness or the ability to feel or experience something, University of California, San Diego neuroscientist Alisson Muotri told Live Science in an email. However, he notes, there is no universally accepted definition.

Some definitions of consciousness focus on the brain's ability to process information and respond to the environment through sensory organs such as vision and hearing. Brain organoids are cultured outside the body and cannot receive such signals, Lavazza noted. However, in the future, more advanced organoids could theoretically experience pain. In humans, the membranes covering the brain, called the meninges, contain neurons capable of sending pain signals to the organ. There is concern that the same could be realized in more complex organoids.

On the other hand, Boyd argued that “if an organoid possesses the internal neural architecture necessary for pain representation, then no external signal is required.” Thus, the presence of a pain signal from a neuron is not necessary for pain to occur; this is precisely how phantom pain occurs in people who have lost limbs.

Wood, however, noted that it's unclear whether the organoid can experience anything like phantom pain, as this may depend on the presence of a memory of the lost limb. In short, it's complicated.

How to measure consciousness?

The article noted that even in humans, scientists lack effective methods for objectively measuring consciousness. Lavazza stated that the only way to accurately determine the presence of consciousness is to ask a person what they are feeling. This doesn't mean that people who are unable to communicate lack consciousness, but it's more difficult to accurately measure.

According to Lomax, for patients in comas or with locked-in syndrome—a neurological disorder that paralyzes the body and severely impedes communication—doctors rely on indirect signals, such as electrical activity in the brain. From this activity, they can only infer consciousness, but not make precise measurements.

An array of microscopic images of chimeroids, a type of brain organoid grown from stem cells from several people.

Another measure includes “perturbative complexity,” which assesses the complexity of brain signals generated in response to a stimulus, such as a magnetic field applied to the scalp. Doctors believe that the more complex the neural activity patterns, the higher the likelihood that the patient is conscious, Lomax said.

However, some indirect signals of consciousness, including perturbative complexity, can be observed even in neurons grown in vitro, he emphasized. This suggests that they are not good indicators of this phenomenon.

Complexity breeds consciousness

Skeptics who doubt that brain organoids can become conscious argue that they lack the necessary anatomical complexity, including a wide range of cell types and blood vessels to deliver oxygen and the resources needed for complex signaling.

But in the next five to ten years, technological advances could allow scientists to create complex organoids with consciousness, Wood said. A study published in August reported a method for introducing blood vessels into brain organoids, while another, published in September, found ways to introduce an additional type of cell called microglia, which cannot be obtained from neural stem cells. Previously, scientists have grown brain organoids with rudimentary “eyes,” while another group of scientists grew organoids with a blood-brain barrier, which helps protect the organ from toxins and pathogens.

Although modern organoids resemble only a single brain region, neuroscientists can group them into “assembloids” representing multiple regions. Lavazza stated that such assembloids are likely capable of feeling pain if they carry the neural network necessary for pain perception—even if they lack pain neurons.

Should the rules change?

Regulations regarding brain organoid research are somewhat lenient, as the International Society for Stem Cell Research (ISSCR) maintains that these structures are incapable of pain perception. Its guidelines state: “There is currently no biological evidence to suggest any issues, such as consciousness or pain perception, in organoids corresponding to CNS [central nervous system] tissues that would require consideration under a specialized oversight procedure.”

However, experts Live Science spoke with agreed that the rules should be revised in light of recent breakthroughs in organoid development.

“This was a very conservative vision of the ISSCR and it needs to be revisited with a multidisciplinary team, not just stem cell biologists,” said Muotri, founder of Tismoo, a company that develops brain organoids.

Ethical concerns are partly related to the organoids' potential ability to feel pain and form their own thoughts. “The well-being of a conscious organoid once created must be considered, as it becomes a morally significant entity with its own interests,” Wood explained.

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Lavazza takes a different stance. “Personally, I don't think it's unethical to grow conscious brain organoids,” he said, adding that “scientists are conducting experiments with other conscious creatures, like mice.” Lomax argued that if brain organoids were to become conscious, they should be subject to the same regulatory oversight as animals undergoing research.

While a lab-grown brain may seem like something out of Brave New World, it could soon become a reality. Assessing consciousness and agreeing on regulations will be challenging, but Wood argues that the burden of proof should lie with the skeptic seeking to disprove consciousness, not the proponent seeking to prove its feasibility.

At the very least, his article says, scientists shouldn't rule out the possibility.

Brain Quiz: Test Your Knowledge of the Body's Most Complex Organ

Kamal Nahas, Social Link Navigation, Live Science Contributor

Kamal Nahas is a freelance writer based in Oxford, UK. His work has appeared in New Scientist, Science, and The Scientist, among other publications. He primarily covers research in evolution, health, and technology. He holds a PhD in pathology from the University of Cambridge and an MSc in immunology from the University of Oxford. He currently works as a microscopist at the Diamond Light Source, a UK synchrotron. When not writing, he enjoys fossil hunting on the Jurassic Coast.

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