In 2008, research into understanding the human brain made an extraordinary breakthrough. Researchers found just the right conditions to coax human stem cells into becoming a miniature lab-grown brain, according to the stem cell biology journal Cell Stem Cell. These brain “organoids” are tiny, measuring ~4 millimeters in diameter and containing 2 million to 3 million cells specific to one brain region, according to Nature. For comparison, an adult human brain contains an estimated 86 billion neurons, with many cell types connected in complex ways across multiple brain regions.

While organoids have been developed for the gut, lung, heart, liver and many other organs, the miniature lab-grown brain organoid has perhaps been the most impactful for biomedical research. Human brain organoids are much less complex than human brains, but they’ve greatly accelerated discoveries about schizophrenia, autism spectrum disorders, Alzheimer’s disease, brain cancers and how the brain is affected by COVID-19 or Zika virus. These conditions do not affect laboratory mice but can have a devastating effect on humans.

Since organoids can be generated from adult skin cells (after they are induced to become stem cells), it’s possible to test potential therapies on a miniature version of a patient’s own tissue. The potential here is huge for future biomedical discoveries, as well, but it raises some interesting questions and ethical concerns.

Can Lab-Grown Brains Become Conscious?

Brain organoids are small because they lack the cells that form blood vessels; however, researchers are developing methods to make lab-grown brains more complex. Brain organoids can be generated for different parts of the brain — such as the forebrain, cerebellum and cerebral cortex — then mixed together to form a more complex structure. Human brain organoids have been transplanted into adult mice, where they made neural connections with the rodent brain cells and acquired blood vessels, as Nature Biotechnical reports.

Cell Stem Cell also describes how the human brain organoids produced coordinated waves of neural activity (EEG patterns), resembling what’s seen in preterm human babies. The waves continued for months before the research group stopped the experiment. This type of brain-wide, coordinated electrical activity is one of the properties of a conscious brain. These results brought urgency to discussions of how to ethically regulate research on organoids, particularly brain organoids.

Can lab-grown brains become conscious? The definition of consciousness varies, even among the scientists and ethicists discussing the issue. Very generally, it means being aware of one’s surroundings. One simple measure of consciousness is the ability to feel pain. The brain does not have pain receptors, but the membranes surrounding the brain do have pain receptors. As brain organoids become more complex, it’s possible these membranes could develop and allow a brain organoid to feel pain.

Detecting light is another way of being aware of one’s surroundings. In 2017, scientists created brain organoids containing photoreceptor cells that responded to light, according to Nature. However, it’s unlikely these organoids could process the visual information, since they lacked the anatomical structures necessary to create complex EEG patterns.

Most neurobiologists don’t believe the currently available brain organoids are conscious. After extensive discussion, the National Academies of Sciences, Engineering and Medicine recently concluded that existing regulations governing stem cell research are currently adequate for overseeing research into brain organoids, per Science. While the prospect of conscious brain organoids still seems far off, the field is moving quickly, and specific regulations should be developed.

Ethics in Animal Research

If consciousness is defined as the ability to feel pain and sense light, then fruit flies, laboratory mice and most other animals are conscious. Nonetheless, animal research is permitted with reasonable restrictions, because the knowledge gained has the potential to significantly improve human life. Research institutions and funding agencies have strict rules for animal care that researchers must follow. With some minor modifications, these rules can also apply to organoid research, as the Cambridge University Press explains.

The basic rules can be considered the three Rs — reduce, refine and replace:

• Reduce the number of potentially conscious brain organoids to the minimum necessary to achieve the research goals.
• Refine the experimental techniques to reduce possible harms (e.g., by administering anesthetic or preemptively using gene editing to reduce the possibility of pain).
• Replace potentially conscious brain organoids with non-conscious organoids or other material, if possible, to achieve the same research goals.

For organoids — especially brain organoids — the potential for improving the human condition is so great that abandoning the research because of a currently theoretical concern may itself be unethical. Even so, it’s worth exploring these questions and agreeing on restrictions and regulations that should be in place to address ethical concerns around brain organoids.

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