Mice have been created whose brains are half human. As a result, the animals are smarter than their siblings. The idea is not to mimic fiction, but to advance our understanding of human brain diseases by studying them in whole mouse brains rather than in dishes. The altered mice still have mouse neurons – the "thinking" cells that make up around half of all their brain cells. But practically all the glial cells in their brains, the ones that support the neurons, are human.
"It's still a mouse brain, not a human brain," says Steve Goldman of the University of Rochester Medical Center in New York. "But all the non-neuronal cells are human." Goldman's team extracted immature glial cells from donated human fetuses. They injected them into mouse pups where they developed into astrocytes, a star-shaped type of glial cell.
Within a year, the mouse glial cells had been completely usurped by the human interlopers. The 300,000 human cells each mouse received multiplied until they numbered 12 million, displacing the native cells.
"We could see the human cells taking over the whole space," says Goldman. "It seemed like the mouse counterparts were fleeing to the margins."
Human astrocytes are 10 to 20 times the size of mouse astrocytes and carry 100 times as many tendrils. This means they can coordinate all the neural signals in an area far more adeptly than mouse astrocytes can. "It's like ramping up the power of your computer," says Goldman.
A battery of standard tests for mouse memory and cognition showed that the mice with human astrocytes are much smarter than their mousy peers. In one test that measures ability to remember a sound associated with a mild electric shock, for example, the humanized mice froze for four times as long as other mice when they heard the sound, suggesting their memory was about four times better. "These were whopping effects," says Goldman. "We can say they were statistically and significantly smarter than control mice."
Goldman first reported last year that mice with human glial cells are smarter. But the human cells his team injected then were mature so they simply integrated into the mouse brain tissue and stayed put. This time, he injected the precursors of these cells, glial progenitor cells, which were able to divide and multiply. That, he says, explains how they were able to take over the mouse brains so completely, stopping only when they reached the physical limits of the space.
To explore further how the human astrocytes affect intelligence, memory and learning, Goldman is already grafting the cells into rats, which are more intelligent than mice. "We've done the first grafts, and are mapping distributions of the cells," he says.
Although this may sound like the work of science fiction – think Deep Blue Sea, where researchers searching for an Alzheimer's cure accidently create super-smart sharks, or Algernon, the lab mouse who has surgery to enhance his intelligence, or even the pigoons, Margaret Atwood's pigs with human stem cells – and human thoughts – Goldman is quick to dismiss any idea that the added cells somehow make the mice more human.
"This does not provide the animals with additional capabilities that could in any way be ascribed or perceived as specifically human," he says. "Rather, the human cells are simply improving the efficiency of the mouse's own neural networks. It's still a mouse."
However, the team decided not to try putting human cells into monkeys. "We briefly considered it but decided not to because of all the potential ethical issues," Goldman says. "It could be difficult to decide which animals to put human brain cells into. If you make animals more human-like, where do you stop?" he says.