Scientists are getting closer to growing human brains in the lab, and it’s spurring an ethical debate over the welfare of these lab-reared tissues.
The debate surrounds “brain organoids,” which are sometimes mistaken for sci-fi-inspired “brains in boxes.” However, these small assemblies of brain tissue grown from stem cells are too simple to function like a real human brain. As such, scientists have assumed brain organoids lack consciousness, which has led to lax research regulations.
“We feel that in the fear of hype and science-fiction inspired exaggeration, the pendulum has swung far too far in the opposite direction,” Christopher Wood, a bioethics researcher at Zhejiang University in China, told Live Science in an email. In a perspective piece published Sept. 12 in the journal Patterns, Wood and his colleagues argued that technological advances may soon lead to the creation of conscious organoids.
The authors say regulations regarding the use of organoids should be reviewed. It would be unethical for a conscious organoid to experience its own thoughts and interests, or to feel pain, said Boyd Lomax, a neuroscientist at Johns Hopkins University.
But reigning in consciousness may not be straightforward.
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Consciousness is difficult to define
The stem cells used to make brain organoids grow side by side and lack complex organization when they’re cultured on a 2D surface, like a dish. But when they’re grown in a solid gel or a spinning bioreactor that keeps the cells aloft, they adopt 3D anatomical networks that resemble what’s seen in an embryonic brain.
Although they develop 3D features, brain organoids are too simple to be conscious, some neuroscientists argue. Consciousness in a real brain arises when different regions of the organ communicate, but organoids resemble only a single part of the brain. And none of these lab-grown minibrains are larger than 0.16 inches (4 millimeters) in diameter, suggesting important faculties for consciousness are missing.
People often think of consciousness in humans or animals as a state of being aware of oneself. However, “we think of consciousness in organoids as a basic level of sensations, the capacity to feel pain and pleasure,” said Andrea Lavazza, a moral philosopher and neuroethicist at Pegaso University in Italy.
Most neuroscientists define consciousness as self-awareness or the ability to feel or experience something, Alysson Muotri, a neuroscientist at the University of California, San Diego, told Live Science in an email. But there is no universal, agreed-upon definition, he said.
Some definitions of consciousness focus on the brain’s ability to process and respond to its environment through senses, like sight and hearing. Brain organoids are cultured outside a body and cannot receive such signals, Lavazza noted. But in the future, more advanced organoids could still theoretically experience pain. In humans, membranes that envelop the brain, called meninges, contain neurons that can send pain signals to the organ. The worry is the same could be possible in more sophisticated organoids.
On the flip side, Boyd argued that “if an organoid has the internal neural architecture necessary for representing pain, then no external signal would be required.” So, there need not be a pain signal from a neuron for pain to occur; this is how phantom pains arise in people who have lost limbs.
Wood noted, however, that it is unclear whether an organoid could experience something tantamount to phantom pain, as this might depend on having a memory of the lost limb. So in a word, it’s complicated.
How do you measure consciousness?
The perspective piece pointed out that, even in humans, scientists don’t have great methods of objectively measuring consciousness. Lavazza said the only way to definitively detect consciousness is to ask a person what they are feeling. That doesn’t mean that people who can’t communicate lack consciousness, but definitively measuring it is more difficult.
In comatose patients or people with locked-in syndrome — a neurological condition that paralyzes the body and makes communication extremely challenging — doctors rely on indirect signals, such as electrical brain activity, Lomax said. Via this activity, they can only infer consciousness, not produce a definitive measurement.
Another measure involves “perturbational complexity,” which assesses the complexity of brain signals produced in response to a stimulus, such as a magnetic field being applied to the scalp. Doctors judge that the more complex the patterns of neuronal firing, the more likely the patient is conscious, Lomax said.
But some indirect signals of consciousness, including perturbational complexity, can be seen even in neurons grown in a dish, he emphasized. That suggests they are not good indicators of the phenomenon.
Complexity begets consciousness
Skeptics who don’t believe brain organoids could feasibly gain consciousness argue that they lack the anatomical complexity required, including a wide variety of cell types and blood vessels to deliver the oxygen and resources needed for complex signaling.
But in the next five to 10 years, technological innovations could enable scientists to create complex organoids capable of consciousness, Wood said. A study published in August reported a method for introducing blood vessels into brain organoids, and one from September found ways to incorporate an additional cell type, called microglia, that can’t be produced from neural stem cells. Previously, scientists grew brain organoids with rudimentary “eyes,” and another group grew some with blood-brain barriers, which help guard the organ from toxins and pathogens.
Although current organoids resemble only one brain region, neuroscientists can fuse them to make “assembloids” representing multiple regions. Lavazza said such assembloids could feasibly feel pain if they carry the neural circuitry required for pain sensation — even if they have no pain-sensing neurons.
Should regulations change?
Rules relating to brain organoid research are lenient in part because the International Society for Stem Cell Research (ISSCR) states that these entities are unable to perceive pain. Its guidelines say, “At this time, there is no biological evidence to suggest any issues of concern, such as consciousness or pain perception with organoids corresponding to CNS [central nervous system] tissues, that would warrant review through the specialized oversight process.”
However, the experts Live Science spoke to agreed that the regulations should be reviewed following recent breakthroughs in organoid development.
“That was such a conservative vision of the ISSCR, and it needs to be revised by a multidisciplinary team, not only stem cell biologists,” said Muotri, who is the founder of Tismoo, a company that develops brain organoids.
The ethical concerns partly relate to organoids potentially being able to feel pain and to form their own thoughts. “The welfare of the conscious organoid, once it is produced, needs to be taken into account, as it has become a morally relevant entity with interests,” Wood explained.
Lavazza takes a different stance. “I personally do not think it would be unethical to grow brain organoids with consciousness,” he said, adding that “scientists do experiments with other conscious entities, such as mice.” Lomax argued that if brain organoids achieve consciousness, they should receive similar regulatory oversight as animals do in research.
Although lab-grown brains might seem like something out of “Brave New World,” they may become a reality soon. Assessing consciousness and agreeing on regulations will be tricky, but Wood argued that the burden of proof should lie with the skeptic who aims to disprove consciousness rather than with the advocate who aims to show it could be feasible.
At the very least, his article pointed out, scientists shouldn’t rule out the possibility.
