Genetic mingling mixes human, animal cells

RENO, Nev. - On a farm about six miles outside this gambling town, Jason Chamberlain looks over a flock of about 50 smelly sheep, many of them possessing partially human livers, hearts, brains and other organs.

Fri, Apr. 29, 2005

PAUL ELIAS

Associated Press

The University of Nevada-Reno researcher talks matter-of-factly about his plans to euthanize one of the pregnant sheep in a nearby lab. He can't wait to examine the effects of the human cells he had injected into the fetus' brain about two months ago.

"It's mice on a large scale," Chamberlain says with a shrug.

As strange as his work may sound, it falls firmly within the new ethics guidelines the influential National Academies issued this past week for stem cell research.

In fact, the Academies' report endorses research that co-mingles human and animal tissue as vital to ensuring that experimental drugs and new tissue replacement therapies are safe for people.

Doctors have transplanted pig valves into human hearts for years, and scientists have injected human cells into lab animals for even longer.

But the biological co-mingling of animal and human is now evolving into even more exotic and unsettling mixes of species, evoking the Greek myth of the monstrous chimera, which was part lion, part goat and part serpent.

In the past two years, scientists have created pigs with human blood, fused rabbit eggs with human DNA and injected human stem cells to make paralyzed mice walk.

Particularly worrisome to some scientists are the nightmare scenarios that could arise from the mixing of brain cells: What if a human mind somehow got trapped inside a sheep's head?

The "idea that human neuronal cells might participate in 'higher order' brain functions in a nonhuman animal, however unlikely that may be, raises concerns that need to be considered," the academies report warned.

In January, an informal ethics committee at Stanford University endorsed a proposal to create mice with brains nearly completely made of human brain cells. Stem cell scientist Irving Weissman said his experiment could provide unparalleled insight into how the human brain develops and how degenerative brain diseases like Parkinson's progress.

Stanford law professor Hank Greely, who chaired the ethics committee, said the board was satisfied that the size and shape of the mouse brain would prevent the human cells from creating any traits of humanity. Just in case, Greely said, the committee recommended closely monitoring the mice's behavior and immediately killing any that display human-like behavior.

The Academies' report recommends that each institution involved in stem cell research create a formal, standing committee to specifically oversee the work, including experiments that mix human and animal cells.

Weissman, who has already created mice with 1 percent human brain cells, said he has no immediate plans to make mostly human mouse brains, but wanted to get ethical clearance in any case. A formal Stanford committee that oversees research at the university would also need to authorize the experiment.

Few human-animal hybrids are as advanced as the sheep created by another stem cell scientist, Esmail Zanjani, and his team at the University of Nevada-Reno. They want to one day turn sheep into living factories for human organs and tissues and along the way create cutting-edge lab animals to more effectively test experimental drugs.

Zanjani is most optimistic about the sheep that grow partially human livers after human stem cells are injected into them while they are still in the womb. Most of the adult sheep in his experiment contain about 10 percent human liver cells, though a few have as much as 40 percent, Zanjani said.

Because the human liver regenerates, the research raises the possibility of transplanting partial organs into people whose livers are failing.

Zanjani must first ensure no animal diseases would be passed on to patients. He also must find an efficient way to completely separate the human and sheep cells, a tough task because the human cells aren't clumped together but are rather spread throughout the sheep's liver.

Zanjani and other stem cell scientists defend their research and insist they aren't creating monsters - or anything remotely human.

"We haven't seen them act as anything but sheep," Zanjani said.

Zanjani's goals are many years from being realized.

He's also had trouble raising funds, and the U.S. Department of Agriculture is investigating the university over allegations made by another researcher that the school mishandled its research sheep. Zanjani declined to comment on that matter, and university officials have stood by their practices.

Allegations about the proper treatment of lab animals may take on strange new meanings as scientists work their way up the evolutionary chart. First, human stem cells were injected into bacteria, then mice and now sheep. Such research blurs biological divisions between species that couldn't until now be breached.

Drawing ethical boundaries that no research appears to have crossed yet, the Academies recommend a prohibition on mixing human stem cells with embryos from monkeys and other primates. But even that policy recommendation isn't tough enough for some researchers.

"The boundary is going to push further into larger animals," New York Medical College professor Stuart Newman said. "That's just asking for trouble."

Newman and anti-biotechnology activist Jeremy Rifkin have been tracking this issue for the last decade and were behind a rather creative assault on both interspecies mixing and the government's policy of patenting individual human genes and other living matter.

Years ago, the two applied for a patent for what they called a "humanzee," a hypothetical - but very possible - creation that was half human and chimp.

The U.S. Patent and Trademark Office finally denied their application this year, ruling that the proposed invention was too human: Constitutional prohibitions against slavery prevents the patenting of people.

Newman and Rifkin were delighted, since they never intended to create the creature and instead wanted to use their application to protest what they see as science and commerce turning people into commodities.

And that's a point, Newman warns, that stem scientists are edging closer to every day: "Once you are on the slope, you tend to move down it."

ON THE NET

NAS: http://www.nas.edu

Zanjani's Web site: http://www.unr.edu/cmbprog/ezanjani-new.htm

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