[Paleopsych] WSJ: Chimeras exist, what if some turn out too human?

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Sat May 7 10:44:55 UTC 2005

Chimeras exist, what if some turn out too human?
5.5.6. I presume this was picked up from the WSJ.

By Sharon Begley, The Wall Street Journal

If you had just created a mouse with human brain cells, one thing you
wouldn't want to hear the little guy say is, "Hi there, I'm Mickey."
Even worse, of course, would be something like, "Get me out of this &
percentGBP !! body!"

It's been several millennia since Greek mythology dreamed up the
chimera, a creature with the head of a lion, the body of a goat and the
tail of a serpent. Research on the chimera front was pretty quiet for
2,500 years. But then in 1984 scientists announced that they had merged
embryonic goat cells with embryonic sheep cells, producing a "geep."
(It's part wooly, part hairy, with a face only a nanny goat could love.)
A human-mouse chimera made its debut in 1988: "SCID-hu" is created when
human fetal tissue -- spleen, liver, thymus, lymph node -- is
transplanted into a mouse. These guys are clearly mice, but other
chimeras are harder to peg. In the 1980s, scientists took brain-to-be
tissue from quail embryos and transplanted it into chicken embryos. Once
hatched, the chicks made sounds like baby quails.

More part-human chimeras are now in the works or already in lab cages.
StemCells Inc., of Palo Alto, Calif., has given hundreds of mice
human-brain stem cells, for instance. And before human stem cells are
ever used to treat human patients, notes biologist Janet Rowley of the
University of Chicago, they (or the cells they develop into) will be
implanted into mice and other lab animals. "The centaur has left the
barn more than people realize," says Stanford University law professor
and bioethicist Henry Greely.

Part-human creatures raise enough ethical concerns that a National
Academy of Sciences committee on stem cells veered off into chimeras. It
recommended last week that some research be barred, to prevent some of
the more monstrous possibilities -- such as a human-sperm-bearing mouse
mating with a human-egg-bearing mouse and gestating a human baby. "We're
not very concerned about a mouse with a human spleen," says Prof.
Greely. "But we get really concerned about our brain and our gonads."

That's why his Stanford colleague, Irving Weissman, asked Prof. Greely
to examine the ethical implications of a mouse-human chimera. StemCells,
co-founded by Prof. Weissman, has already transplanted human-brain stem
cells into the brains of mice that had no immune system (and hence
couldn't attack the foreign cells). The stem cells develop into human
neurons, migrate through the mouse brain and mingle with mouse cells.
The human cells make up less than 1 percent of the mouse brain, and are
being used by the company to study neurodegenerative diseases.

But Prof. Weissman had in mind a new sort of chimera. He would start
with ill-fated mice whose neurons all die just before or soon after
birth. He planned to transplant human-brain stem cells into their brains
just before their own neurons died off. Would that lead the human cells
to turn into neurons and replace the dead-or-dying mouse neurons,
producing a mostly human brain in a mouse?

Such a chimera could bring important scientific benefits. The SCID-hu
mouse, though it hasn't yielded a cure for AIDS, has been "a very
valuable animal model," says Ramesh Akkina of Colorado State University,
Fort Collins, who directs a lab that uses this part-human mouse. "It has
human T cells circulating, which will allow us to test gene therapy for
AIDS" in a way that will be more relevant to patients than all-animal
models. The co-creator of SCID-hu, Michael McCune of the Gladstone
Institute of Virology and Immunology, San Francisco, notes that because
the human organs last for months in the mice (they would die in days in
a lab dish), "it is possible to study the effects of HIV" in many kinds
of human cells in a living system.

Similarly, studying living human neurons in a living mouse brain would
likely yield more insights than studying human neurons in a lab dish or
mouse neurons in a mouse brain. "You could see how pathogens damage
human neurons, how experimental drugs act, what happens when you infect
human neurons with prions (which cause mad-cow disease) or amyloid
(associated with Alzheimer's)," says Prof. Greely. "The big concern is,
could you give the mouse some sort of human consciousness or

"All of us are aware of the concern that we're going to have a human
brain in a mouse with a person saying, 'Let me out,'" Prof. Rowley told
the President's Council on Bioethics when it discussed chimeras in

To take no chances, scientists could kill the mice before birth to see
if the brain is developing mouse-y structures such as "whisker barrels,"
which receive signals from the whiskers. If so, it's a mouse. If it is
developing a large and complex visual cortex, it's too human. "If you
saw something weird, you'd stop," says Prof. Greely. "If not, let the
next ones be born, and examine them at different ages to be sure they're
still fully mouse."

To reduce the chance that today's chimeras will be as monstrous as the
Greeks' were, the U.S. patent office last year rejected an application
to patent a human-chimp chimera, or "humanzee." But that, of course,
just keeps someone from patenting one -- not making one.

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