[Paleopsych] Monterey Herald: Genetic mingling mixes human, animal cells

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Mon May 2 16:23:14 UTC 2005

Genetic mingling mixes human, animal cells

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.

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

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

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

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."

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