Prof. plans to put human cells in mouse brains

Irving Weissman, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, has worked with the transfer of human neurons to the brains of mice for several years now. He has already bred mice whose brains are composed of 1 percent human neurons, finding that transplanted human brain cells could successfully connect to a mouse brain.

“Remarkably, even though humans and mice are separated by millions of years of evolution, human neurons responded to the mouse signals,” Weissman said.

Now, he wants to initiate a new experiment by transplanting human brain-stem cells to an inbred strain of mice whose natural brain cells die before the mice’s birth. Human brain cells would then replace the mice’s own, creating a breed of mice whose brains are composed entirely of human neurons.

Although Weissman acknowledged that the experiment “may not even work at all” — if it were to be successful, scientists would have a way to study living human-brain cells in a lab animal. Researchers, according to Weissman, would then be able to experiment on diseased human neurons in lab animals in ways that they could not with human subjects due to the high risks.

But even with the potential benefits, blurring the line between species has always brought up many ethical concerns in the scientific community, as well as negative reactions from the public.

As part of an ethics committee gathered together by Weissman, Stanford Law Prof. Henry Greely has identified four ethical questions concerning the project. They include the use of stem cells from aborted fetuses, the inappropriate use of human tissue and the pain and suffering of the laboratory mice.

However, the main concern, Greely said, is “running the risk of conferring aspects of humanness in the mice.”

In other words, the creation of a human chimera — a mouse with human consciousness.

In Greek mythology, chimeras were hybrid creatures with bodies of goats, heads of lions and tails of snakes. But both Weissman and Greely agreed that the project in question is nowhere near so sensational.

This past July, Sen. Sam Brownback (R-Kan.) introduced a bill to prohibit the creation of human chimeras. If passed, the new legislation would ban experiments like Weissman’s, even making them subject to criminal penalty.

“If passed, the legislation might make it a 10-year prison sentence to conduct experiments like these,” Greely said.

He also mentioned that the strongest reaction from the public to human chimeras is usually the “yuck factor.”

“People have talked about giving this mouse a human brain, but that would not be true,” Greely said. “It would be unlikely to truly impossible for these mice to exhibit human ability.”

He stressed that neurons only comprise about 10 percent of the brain, while the connections between neurons are what scientist believe determine consciousness. Greely described neurons as the bricks that make up the brain.

“A church built with red bricks instead of gray will still be a church because the framework has not changed, just as the structure of the mouse’s brain has not changed,” he said. “What’s important is the architecture, not the bricks.”

Stanford students surveyed also doubted the possibility of someone creating a “Stuart Little.”

“I’d be interested to see the results of the experiment, but I don’t think the mouse is going to get up and start talking,” said freshman Jonathan Scrafford. “But if it did, then it would raise some issues.”

Others said they did not believe the experiment raised any serious ethical questions.

“It doesn’t bother me that much,” said junior Daniel Jacobs. “Even if the worst thing happened and all the human behavior was transferred to a mouse, it wouldn’t be that bad.”

Junior Andrew Liefer, the technology columnist for The Daily, said he had mixed feelings about the experiment.

“All this research is good because it’s helping solve a lot of problems, but it’d be nice if people thought about the ethical concerns a little more,” he said.

Greely’s recommendation to Weissman was to forge ahead step-by-step and to look for humanness in the structure of the mouse brain before proceeding further.

“If everything looks mouse-like, go forward. If anything looks un-mouselike, stop,” he said.

But at the moment, Weissman’s proposed mouse project still has not begun as he waits for the scientific community’s approval after reviewing the ethical concerns raised by the experiment.

“This project will test human neuronal cells in a mouse brain micro-environment as a prelude to studying stem cells that have human genetic diseases like Alzheimer’s, Parkinson’s, Lou Gehrig’s, and cerebral palsy,” Weissman said.

Weissman emphasized the urgency of his project as he asked, “Which of these diseases should we not be working on as fast as we can?”