By Mihaela Bozukova. Mentored and edited by Suresh Vandana.
While animal models have paved much of the way to unraveling the biological underpinnings of neurological diseases, the complexities of the human brain are never fully captured by these models.
In a session on the trends in neuroscience research and their societal impacts at the 2022 American Association for the Advancement of Science (AAAS) annual meeting, a panel of experts discussed the merits and possible ethical concerns of using human brain-inspired experimental models to study neurological diseases.
“Our genome is unique, and we don’t understand yet how a specific genome context can be associated with disease of the [human] brain,” said Paola Arlotta of Harvard University.
Enter brain organoids. These 3-dimensional aggregates of brain cells are made by exposing donated human blood or skin cells to a cocktail of chemicals, reprogramming them to a stem cell-like state. With the power to differentiate, these stem cells can be made to transform into different cell types of the human brain. Over time, these newly formed brain cells clump together, creating 3D structures that closely resemble actual brain tissue.
And these organoids hold great promise. For one, scientists can now study how the human brain develops during very early embryonic stages, which has so far been a challenge. In addition, the organoids’ closer approximation of the human brain gives scientists a realistic, yet tractable platform to study neurological diseases without probing the organ directly.
As an example application of brain organoids in neuroscience research, Arlotta highlighted her current work using these model systems to investigate how certain genes may contribute to the development of autism. Her team designed brain organoids carrying three genetic mutations commonly observed in people with this neurological disorder. They found that the three mutations could individually affect the developmental timelines of different classes of neurons in the brain.
“Now, we have an opportunity to understand how we get the brain that we get,” said Arlotta. “Perhaps most importantly we can now have a human model for some of the most devastating neurological diseases that affect society.”
While there is considerable excitement around brain organoid research, the panelists also acknowledged the ethical concerns that have come with it, particularly as it relates to consciousness, awareness and pain.
After all, are brain organoids commensurate to miniature human brains in a dish?
“Mini brains evoke all kinds of emotional responses in people. But the term itself is misleading and inaccurate,” said Bernard Lo, professor of medicine emeritus from The University of California, San Francisco, and a co-panelist.
Brain organoids, he said, are still reductionist experimental models. While scientists can stitch up organoids created to resemble different brain regions to build larger structures, such connectivity is very primitive and does not compare to the complexity of actual neuronal networks across different parts of the human brain.
Despite the simplicity of current brain organoids, Arlotta emphasized the importance of constant and clear communication as the field of brain organoids progresses, so that scientists, scholars and society at large can collectively assess its benefits and concerns.
“Now is the time to address ethical concerns and start public engagement and interdisciplinary dialogues, and to build the foundation for reassessing oversight policies as the science develops,” said Lo.
Mihaela Bozukova recently obtained her Ph.D. in epigenetics from the Max Planck Institute for Biology of Ageing in Germany. She is also a freelance science writer and scientific social media manager. Get in touch with her on Twitter @MBozukova or via email at mihaela.bozukova@gmx.net.
Photo: Neural organoids are a promising new model to study brain development and neurological disease. Credit: Max Pixel
