Cell Alchemy
By Jane Palmer

The fluorescent-green trace spiked, plunged, then flattened into a long, unwavering horizontal line. But the waveform’s demise didn’t mark the end of a life, just the end of a conversation.

Two cells from humble beginnings had just finished saying their piece.

“Not only do they look like neurons, they act like neurons,” said Tommy Vierbuchen, a Stanford University graduate student, talking about the cells’ ability to form connections and communicate. “They’ve passed all the tests we have thrown at them so far.”

Sophisticated, sociable cells are the end product of Vierbuchen’s invention. In late 2009, after months of experimentation, he perfected a technique for transforming skin cells taken from the tails of mice directly into precious neuron-like cells, termed induced neuronal (iN) cells.

“What makes the this so interesting is the potential use for these cells for therapeutic purposes or disease modeling,“ said Arnold Kriegstein, director of the Institute for Regeneration Medicine at the University of California, San Francisco.

Earlier in 2009, Vierbuchen had discovered that adding 19 genes involved in neural development and function to a culture of mouse embryo skin cells produced a few cells that resembled immature neurons.

“It was certainly exciting,” said Vierbuchen, a self-confessed worrier. “But we wouldn’t have been able to convince anyone that these were really neurons.”

Inspired by the result, Vierbuchen then set to the task of creating true neuron-like cells. Yet his final invention was so simple it belied the months of imagination and complex deduction needed to create it. The technique uses just three genes -- Ascl1, Brn2, and Myt1l -- to convert ordinary skin cells into induced iN cells in merely two weeks.

“You could call it a landmark study,” said Kriegstein. “It has certainly seemed to generate a great deal of interest.”

If the technique works for human cells, it could provide a more efficient way of investigating neurological diseases, Vierbuchen said. Studying the underlying biological basis of disorders, such as Parkinson’s and autism, has always proved difficult. “You can’t just take neurons out of the brain,” he said.

If scientists can use the skin cells of patients to create iN cells, they could get a unique perspective on the brain tissue associated with these disorders and possibly design drugs or treatments. Also, healthy iNs could be used to repair brains damaged by disease or injury, Kriegstein said.

That his invention could end up helping patients is very satisfying, Vierbuchen said. He was drawn to biological research because he wanted to do hands-on work that had important implications for human health. True to purpose, he now remains focused on developing his technique for human cells. “It is what everyone wants to see next so we are working on it,” he said.

But are his motives entirely altruistic?

“I think it is really exciting to do something that no one has done before,” Vierbuchen admitted. At last, he relaxes and smiles. “You’d be lying if you said that wasn’t your motivation.”