Arguably, the greatest frontier in biomedical research is our understanding of the human brain. While we are making strides in mapping circuits in the brain and understanding how different areas of the brain function and contribute to different neurological diseases, overall the brain is still a huge mystery. Over many years, most of the knowledge we have gained about the brain has come from the use of animal models, which offer a glimpse into how the brain functions. However, no animal’s brain is quite like the human brain in terms of sophistication and complexity, so there are major gaps in our research. 

One method that is extending our understanding of the human brain is the use of stem cells, which can be coaxed into producing pea-sized collections of brain tissue — a mini-brain of sorts. Certain stem cells can develop into any cell in the body, including brain cells. Researchers can culture these cells to become brain cells by stimulating them with molecules called growth factors. To grow the cells, researchers use a bioreactor, which is an incubator containing the right environment and nutrients for cell growth.

After a few weeks in the bioreactor, the stem cells grow into small clumps of brain tissue called organoids. These organoids contain different types of nerve cells: they have the characteristic electrical activity of the brain and they have a structure that includes the typical six layers of the cortex of the human brain. The cortex is the outermost layer of the brain, responsible for higher activities such as speech, judgement and other cognitive functions. The similarities between the organoids and a normal human brain allow sophisticated studies to be conducted in the laboratory.

Until recently, these mini-brains were studied exclusively in the lab in a bioreactor, where they have yielded new information on conditions from Alzheimer’s disease to the Zika virus. Now several research groups have implanted these pea-sized organoids into the brains of experimental lab rats and mice. With implantation, the organoids connect to the animal’s blood supply, which allows them to grow larger and integrate into the animal’s brain function. This could be a new model of how the human brain works and a refined way to explore brain disorders such as autism.

Research has already shown that the organoid tissue cells extend into the surrounding mouse brain, interconnecting the human and mouse brain tissues. No one has determined whether the animal’s intelligence or level of consciousness changes. It seems unlikely, as the amount of human brain tissue is so small, and the total amount is a fraction of what we observe in an infant. But this is sounding alarms – when might the threshold be crossed to give an animal some human characteristics? When would an animal become too human? Our scientific progress may have surpassed our ethical scaffolding and regulatory network. This will remain an area of intense debate with ethicists and scientists. Either way, we will continue to explore the human brain and define what it means to be human.


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