of mice and men

Mice Created With Human Brain Cells
- By PAUL ELIAS, AP Biotechnology Writer
Monday, December 12, 2005

(12-12) 14:59 PST San Francisco (AP) --

Add another creation to the strange scientific menagerie where animal species are being mixed together in ever more exotic combinations.

Scientists announced Monday that they had created mice with small amounts of human brain cells in an effort to make realistic models of neurological disorders such as Parkinson's disease.

Led by Fred Gage of the Salk Institute in San Diego, the researchers created the mice by injecting about 100,000 human embryonic stem cells per mouse into the brains of 14-day-old rodent embryos.

Those mice were each born with about 0.1 percent of human cells in each of their heads, a trace amount that doesn't remotely come close to "humanizing" the rodents.

"This illustrate that injecting human stem cells into mouse brains doesn't restructure the brain," Gage said.

Still, the work adds to the growing ethical concerns of mixing human and animal cells when it comes to stem cell and cloning research. After all, mice are 97.5 percent genetically identical to humans.

"The worry is if you humanize them too much you cross certain boundaries," said David Magnus, director of the Stanford Medical Center for Biomedical Ethics. "But I don't think this research comes even close to that."

Researchers are nevertheless beginning to bump up against what bioethicists call the "yuck factor."

Three top cloning researchers, for instance, have applied for a patent that contemplates fusing a complete set of human DNA into animal eggs in order to manufacturer human embryonic stem cells.

One of the patent applicants, Jose Cibelli, first attempted such an experiment in 1998 when he fused cells from his cheek into cow eggs.

"The idea is to hijack the machinery of the egg," said Cibelli, whose current work at Michigan State University does not involve human material because that would violate state law.

Researchers argue that co-mingling human and animal tissue is vital to ensuring that experimental drugs and new tissue replacement therapies are safe for people.

Others have performed similar experiments with rabbit and chicken eggs while University of California-Irvine researchers have reported making paralyzed rodents walk after injecting them with human nerve cells.

Doctors have transplanted pig valves into human hearts for years, and scientists have injected human cells into lab animals for even longer. But the brain poses an additional level of concern because some envision nightmare scenarios in which a human mind might be trapped in an animal head.

"Human diseases, such as Parkinson's disease, might be amenable to stem cell therapy, and it is conceivable, although unlikely, that an animal's cognitive abilities could also be affected by such therapy," a report issued in April by the influential National Academies of Science that sought to draw some ethical research boundaries.

So the report recommended that such work be allowed, but with strict ethical guidelines established.

"Protocols should be reviewed to ensure that they take into account those sorts of possibilities and that they include ethically sensitive plans to manage them if they arise," the report concluded.

At the same time, the report did endorse research that co-mingles human and animal tissue as vital to ensuring that experimental drugs and new tissue replacement therapies are safe for people.

Gage said the work published Monday in the journal Proceedings of the National Academy of Sciences is another step in overcoming one of the biggest technical hurdles confronting stem cell researchers: when exactly to inject the cells into patients.

The results suggest that human embryonic stem cells, once injected into people, will mature into the cells that surround them. No known human has ever received an injection of embryonic stem cells because so little is known about how those cells will mature once inside the body.

For now, Gage said his work is more geared toward understanding disease than to finding a cure.

"It's a way for us to begin to tease out the way these diseases develop," Gage said.

Human embryonic stem cells are created in the first days after conception and give rise to all the organs and tissues in the human body. Scientists hope they can someday use stem cells to replace diseased tissue. But many social conservatives, including President Bush, oppose the work because embryos are destroyed during research.

Stem cell researchers argue that mixing human and animal cells is the only way to advance the field because it's far too risky to experiment on people; so little is known about stem cells.

"The experiments have to be done, which does mean human cells into non-human cells," said Dr. Evan Snyder, a stem cell researcher at the Burnham Institute in San Diego. "You don't work out the issues on your child or your grandmother. You want to work this out in an animal first."

Snyder is injecting human embryonic stem cells into monkeys and is convinced that there's little danger.

"It's true that there is a huge amount of similarity, but the difference are huge," Snyder said. "You will never ever have a little human trapped inside a mouse or monkey's body."

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On the Net:

Gage lab:

Stanford ethics center:

NAS:

www.salk.edu/faculty/faculty/details.php?id23

scbe.stanford.edu/research/

http://national-academies.org/


URL: http://sfgate.com/cgi-bin/article.cgi?file=/news/archive/2005/12/12/national/a141612S53.DTL