Unraveling the Mysteries of the Human Brain: The Promise of Brain Organoids
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Most of our ‘knowledge’ about the human brain has come from the study of the mouse brain. A neuroscientist dissects mouse brains, hoping to find out more about their major regions and important structures associated with mental and neurological disorders – such as autism or epilepsy – and how to fix them. The knowledge so gained is then applied to treat human patients because the human brain is quite similar to the mouse brain. However, these two species have evolved in different ways, adapting the brain of each for their respective lifestyles and evolutionary niches. This explains why cures in mice don’t always translate into cures for humans. Indeed, our reliance on the mouse has left us with many unanswered questions, such as when the first human neuron fires.
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While we normally use non-invasive techniques such as ultrasound to visualise the developing foetal brain, we can’t experimentally investigate it at a resolution that allows us to understand it. It is not possible to invasively study a human embryo inside the womb. Neuroscientific research would gain much if researchers could study a human brain that is not inside a human being. Fortunately in 2008, the Japanese researcher Yoshiki Sasai discovered that it was possible to cultivate artificial human neural tissues outside the womb. So-called ‘pluripotent’ stem cells have the ability to generate cell types for all tissues in the human body. You can get pluripotent stem cells from the human embryo, or by reprogramming cells from a more developed organism. Sasai has shown that one can guide these cells – independent of their origin – to become a neural tissue by exposing them to specific external factors. When suspended in liquid, these neural-committed cells spontaneously self-aggregate, and form small, organized three-dimensional clusters that resemble the anatomic structure of the foetal human brain. We now call these structures ‘brain organoids’ or ‘mini-brains’.
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These brain organoids can grow up to 0.5 cm, a pea-sized body of white tissue that you can see with the naked eye. They are kept floating in a juicy, reddish stew that contains all the nutrients the cells need to survive. And, indeed, they can survive for weeks, months and years. Some have even survived three full years – and it seems they could be kept alive even longer than that, if someone replaces the juice continuously. After keeping brain organoids alive for several months, scientists observed the spontaneous emergence of brain oscillatory waves in them, similar to those detected by electroencephalograms (EEG). These oscillatory waves are ubiquitous in all living human brains, but were never before recorded emerging from any living human-made system. In other words, this simplistic model of the human brain could – in some ways – recreate the organized formation of the networks that arise in the womb. It shouldn’t be forgotten that brain organoids aren’t actually miniaturized human brains in a dish. Nonetheless, this reductionist human brain model was crucial in helping us figure out that the Zika virus was the culprit behind the outbreak of congenital brain defects in the northeast of Brazil in 2015.
