The Sacramento Bee
Stem cell  team avoids ethics tangle:
Long-running Nevada research makes strides using
human placental blood, not embryos.
By Edie Lau - Bee Science Writer
(Published Aug. 19, 2001)

Scoot over, Dolly. A flock of sheep growing in Reno may be
as biologically astonishing as the Scottish sheep clone.

Inside the white, fleecy bodies of the Nevada sheep is
evidence of the power of stem cells. The animals look and
bleat like regular sheep, but they're composed partly
of human cells. There are human cells in their livers,
their hearts, their lungs, their skin, in the linings of their
guts, and even in their brains.

These human-sheep chimeras, as they're called, were
brought to life with funding from the U.S. government.
A long-term goal of the research is to find ways to repair
defects in babies in the womb.

The difference between this University of Nevada, Reno,
research on stem cells and the studies that have elicited
so much debate recently is that the human components
of the sheep came from stem cells derived not from embryos,
but from blood in human placentas.

"It's really an amazing thing," said Esmail Zanjani,
the professor of medicine and physiology who leads the
Reno studies demonstrating the broad versatility of the
neonatal stem cells. "They really have tremendous
potential."

Stem cell research is one of the hottest fields in
medicine  --  and a hot potato politically and ethically.
Stem cells are immature cells in the body that have the
ability to develop into a variety of cell types with
specific functions. Theoretically, the cells could be
manipulated to repair diseased or injured organs
and tissues.

The body possesses stem cells at all stages of development,
from before birth to death. The cells have been found in
bone marrow, the blood of placentas and umbilical cords,
and in embryos. Generally, it's been thought that embryos
yield the most malleable  --  and therefore the most
promising  --  cells, and there is the rub: Gathering the
cells kills the embryo.

Some people who object to using embryonic stem cells
support as an alternative research using stem cells from
the blood of placentas and umbilical cords, arguing they
may be just as useful. These cells typically are discarded
with the rest of the afterbirth following a baby's delivery.

Advocates of placental stem cell research include the
Vatican, which is supporting a new placental/cord blood
bank at Sacre Cuore University in Rome, and President
Bush, who cited the possible value of umbilical cord
and placental stem cells when he announced this month
that limited federal funding would be available for
embryonic stem cell research.

Bush decided that only studies using existing lines of
embryonic cells may obtain taxpayer money. So far,
there's been little controversy over research on stem cells
from animals other than humans, from human adults,
and from afterbirth  --  these studies have been funded
all along.

Zanjani, in Reno, said he has received grants from the
National Institutes of Health for 30 years. His experiments
in making human-sheep chimeras, which began 12 years
ago, largely are supported by the federal government,
on the order of $200,000 to $300,000 a year, he said.

The injection of human placenta stem cells into sheep
demonstrates that stem cell research not involving embryos
can raise tough ethical questions, as well.

At the very least, "this one scores high on the 'yuck' factor,"
said Arthur Caplan, a bioethicist at the University of
Pennsylvania and frequent commentator on cloning,
stem cells, artificial reproduction and related topics.

"We think about Minotaurs and centaurs, where they've
got human heads on animal bodies," Caplan said.
But from a biologist's point of view, he said, putting
animal cells in people or vice versa "is more or less trivial,
unless they're carrying a (disease)."

Biologists use the term "chimera" to describe an organism
with two or more genetically different cell types.
In Greek mythology, chimeras are monsters.

Zanjani, an easygoing man with a quick smile and a cap
of snowy hair, expresses no doubts about the
appropriateness of his work.

"We're not doing anything bad," he said. "What we do
even the anti-abortion people like because what we're
trying to do is save babies."

The aim of Zanjani's research is to develop strategies
for correcting genetic defects in babies before they're
born. He and his colleagues hope healthy stem cells
eventually could be injected into unhealthy human
fetuses and used by their bodies.

To test the safety and efficacy of the procedure, Zanjani
first is experimenting with laboratory animals.
He is interested in determining whether it's possible
to successfully transplant stem cells into fetuses,
and whether those cells can be used to heal.

He first experimented with transplanting sheep bone
marrow stem cells into the bellies of fetal lambs, and
then turned to cells from human bone marrow.

In the blood and bone marrow of the resulting lambs,
the researchers found human cells. The cells were
functioning  -- producing human proteins  --  and the
sheep were OK.

"They have no illness (resulting from the transplants),
they act like sheep, they're cute as anything," Zanjani
said.

His team has gone on to transplant human placental/cord
blood stem cells into fetal lambs, producing more than
1,500 human-sheep chimeras. The cells are taken up
by the fetuses and appear to be incorporated seamlessly
into their bodies. The lambs are injected at the end of the
first trimester in gestation, when their immune systems
can be fooled into accepting the foreign cells as their own.

Might the presence of a few human neurons in the sheep
give them humanlike minds? Zanjani can't say.

"They don't talk," he jokes.

They sheep are kept in pens and pastures with views
of the eastern Sierra. The scientists are monitoring
some of the sheep for their lifetimes (up to 14 years)
to see whether the human cell grafts remain stable
and functional. Zanjani estimates that the sheep have
2 percent to 3 percent human cells overall, with some
organs possessing a greater percentage.

He said he would not try to significantly boost the
share of human cells. "I don't think that's compatible
with the animals' life," he said.

The Rev. Charles S. McDermott, who handles medical
ethics questions for the Catholic Diocese of Sacramento,
said the ethical propriety of the procedure is, to his mind,
not a matter of absolutes, but of proportion.

The operative question is: Does such research create
a human hybrid?

Deciding what proportion of human cells would
constitute a hybrid is for scientists and ethicists
to work out together, McDermott said. "I would say
that the lower the number of cells, the less unacceptable
it would be."

Zanjani's sheep are unusual for possessing functioning
human cells over the long term, but they are not unique
as experimental animals injected with human cells.

Marcus Muench, a hematology researcher at the
University of California, San Francisco, has contributed
to studies testing human blood stem cells in mice.
Muench said others have done similar work, but to date
no one has grown human cells in another animal species
to the extent Zanjani's team has.

Other types of animal chimeras have been made for years
in the study of developmental biology. Gary Anderson,
chairman of the animal science department at the
University of California, Davis, said that in 1980, he and
colleagues combined a sheep embryo with a goat embryo.
"You get a normal critter that has patches of wool,
patches of hair," he said.

Apart from the ethical questions, the human-sheep chimeras
are a scientific feat. They suggest that stem cells from the
blood of placentas and umbilical cords may be almost as
versatile as embryonic stem cells, able to develop into a
variety of cell types.

For years, it was thought that stem cells, except for those
from an embryo, could generate only a particular kind of cell.
So blood stem cells (those from bone marrow as well as
placentas) would make only blood cells, liver stem cells
liver cells, gut-lining stem cells gut-lining cells, and so on.
But recent studies suggest that these stem cells may be
more flexible.

It was thought, too, that people didn't grow any more
brain cells after birth, but that's become outdated dogma.
Now, the search is on for the source of neuronal stem cells.

The creation of Dolly the sheep contributed profoundly
to the understanding that old cells can be taught new
lessons. Born in 1996, Dolly was the first animal cloned
from an adult cell  --  a 6-year-old udder cell.

Placentas, as almost limitless sources of neonatal blood
and tissue, are an increasingly popular focus of research.
The biotech company Anthrogenesis Corp. in New Jersey
has hooked up placentas to "life support" machinery
in an attempt to find and cultivate stem cells from the
tissue itself, not the blood.

Whatever the ultimate utility of the cells, research with
them is a potentially big business. In Rancho Cordova,
the company Thermogenesis makes kits to collect
placental/cord blood, along with robotic freezers for storage.
A unit able to hold the blood of 3,626 placentas
sells for $200,000. Among customers requesting a quote
on a Thermogenesis system, said CEO Phil Coelho,
is the Vatican, for its new cord blood bank.

The growing profile of placental stem cells is good
for the company, Coelho said. "We think it is likely
that it will be the preferred source of stem cells."

The Bee's Edie Lau can be reached at (916) 321-1098
or [log in to unmask]

SOURCE:  The Sacramento Bee
http://www.sacbee.com/news/news/local02_20010819.html

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