By reprogramming skin cells into brain cells, scientists gain new insights into mental disorders

FOR MANY POORLY UNDERSTOOD MENTAL DISORDERS, such as schizophrenia or autism, scientists often wish they could turn back the clock to uncover what has gone wrong in the brains of these patients, and how to right it before much brain damage ensues. But now, thanks to recent developments in the lab, that wish is coming true.

Researchers are using genetic engineering and growth factors to reprogram the skin cells of patients with schizophrenia, autism, and other neurological disorders and grow them into brain cells in the laboratory. There, under their careful watch, investigators can detect inherent defects in how neurons develop or function, or see what environmental toxins or other factors prod them to misbehave in the petri dish. With these “diseases in a dish” they can also test the effectiveness of drugs that can right missteps in development, or counter the harm of environmental insults.

“It’s quite amazing that we can recapitulate a psychiatric disease in a petri dish,” says neuroscientist Fred (Rusty) Gage, a professor of genetics at the Salk Institute for Biological Studies and member of the executive committee of the Kavli Institute for Brain and Mind (KIBM) at the University of California, San Diego. “This allows us to identify subtle changes in the functioning of neuronal circuits that we never had access to before.”

Below is an edited transcript of a conversation with Gage and Anirvan Ghosh, a neurobiologist at the University of California, San Diego and also an executive committee member of KIBM. Both researchers are on the cutting edge of disease-in-a-dish modeling of neurological disorders. Gage and Ghosh discuss how human skin cells induced to return to an immature state (“induced pluripotent stem cells” or IPS cells) are revolutionizing our understanding and treatment of mental and neurodegenerative disorders, such as Parkinson’s disease, as well as leading to new models of drug development for all diseases.

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