The Washington Post
 August 24, 2001, Friday, Final Edition
SECTION: A SECTION; Pg. A01
HEADLINE: Stem Cell Research Faces FDA Hurdle; With Mouse Cell Base,
Tough Rules Apply
BYLINE: Justin Gillis and Ceci Connolly, Washington Post Staff Writers

"    Most or all of the human embryonic stem cell colonies approved for
research
funding under a new Bush administration policy have been mixed in the
laboratory
with mouse cells, which may create substantial hurdles for scientists
trying to
turn the colonies into treatments for Parkinson's disease, spinal-cord
injuries
and other ailments.

    The cell colonies, or "lines," were created for early-stage research
with no
thought that they would become the only embryonic cells eligible for
federal
money. But that is the status President Bush conferred on them in his
first
prime-time address to the nation on Aug. 9.

    The standard technique for creating human embryonic stem cell lines
has been
to extract cells from inside a microscopic embryo, then grow them atop
embryonic
mouse cells, known as "feeder" cells. The latter excrete some unknown
nutritional or growth factor that helps the human cells stay healthy.
Because
they have been in close contact with mouse cells, the human cells pose a
small
but real risk of transferring potentially deadly animal viruses to
people.

    Because of that, under guidelines the Food and Drug Administration
has been
developing for several years, it would be difficult, though not
impossible, to
use the cells in human clinical tests.

    Under the FDA rules, which are designed to prevent the accidental
creation
of a new plague, transplants of these embryonic cells into people would
be
treated as though they were "xenotransplants," or transplants of animal
tissue.
The guidelines impose stringent requirements on researchers and patients
alike.
They would likely rule out some groups of patients who might otherwise be
eligible to participate in human stem cell tests -- notably, for
instance, young
diabetes patients whose disease can be treated in other ways.

    The human embryonic stem cell lines reported in scientific literature
were
all grown in direct contact with mouse cells and might have picked up
mouse
viruses, which government officials acknowledged would bring them under
the FDA
policy.


 PAGE 2
                      The Washington Post, August 24, 2001

    Scientists are working on ways to grow human embryonic cell lines
without
using mouse cells, but any created after Bush's speech Aug. 9 would be
ineligible for federal research money.

    Patient groups and people who work with them expressed concern when
told
about the xenotransplant restrictions.

    "This would be the exclamation point" on an already lengthy list of
questions about the quantity and quality of the cell lines eligible for
research
funding under the Bush policy, said Kevin Ryder, a consultant to the
American
Cell Therapy Research Foundation, a New York foundation that supports
research
into many types of treatments using cells. "We would have a very
difficult time
getting those advanced into the clinical setting unless we get the FDA to
make
some exceptions down the road."

    Most people on Capitol Hill are unaware of the issue, but as word of
it
began spreading late yesterday, some legislators expressed concern. "The
president's going to have to make available lines of stem cells that will
be
available for the full measure of research anticipated," said Sen. John
F. Kerry
(D-Mass.) "If he doesn't, Congress will need to act to make that happen."

    Jay Lefkowitz, a White House adviser who helped craft the Bush
policy, said
the administration was aware that the stem cell lines Bush approved for
funding
had been mixed with mouse cells and would come under the FDA's
xenotransplant
rules.

    The White House concluded that the issue would not be a serious
barrier at
this stage, when scientists still need to do several years of fundamental
laboratory work before human tests can begin, he said. By the time
researchers
are ready to begin those tests, he said, officials are confident that
scientists
will have found a way to grow stem cells without mouse cells, or will be
able to
work within the FDA's guidelines.

    "President Bush has unlocked the door so that critical, basic
research can
be conducted in an area that is currently uncharted," Lefkowitz said. "To
fulfill that mission, we believe the existing stem cell lines are more
than
adequate."

    Opinion among scientists is mixed about how much of a problem the
xenotransplant issue will be, but at the least, they say, it presents yet
more
practical difficulties in the execution of a policy already rife with
them.

    In the 15 days since Bush announced his policy, other lingering
questions --
about how many cell lines exist, who owns them and how accessible they
will be
to academic scientists -- have gone largely unanswered by the National
Institutes of Health and the Department of Health and Human Services. NIH
administrators are negotiating with companies and labs to try to work out
many
of the details. Congressional hearings are scheduled in two weeks.

    In an interview, a senior NIH administrator and an FDA regulator
acknowledged that the xenotransplant issue could pose hurdles but said it
was
premature to speculate about how serious those might be.

    "There is so little experience with these cells," said Lana Skirboll,
director of science policy at the NIH. "There's a lot that needs to be
done. I

 PAGE 3
                      The Washington Post, August 24, 2001

just think the scientific community is in a position that we have a lot
more to
learn."

    FDA administrators who developed the xenotransplant policy declined
to
comment. But they pointed to written reports and meeting transcripts
going back
five years that make their position clear. The documents, posted on the
Internet, leave little doubt that stem cells grown by current techniques
would
be covered. Although the guidelines are not final, officials said the
agency has
been following them.

    Some laboratories that work with stem cells appear to be unaware of
the
policy; others are operating under the assumption that it will be a large
hurdle
in creating treatments from any of the existing cell lines. "It could be
a real
killer," said George Daley, a stem cell researcher at the Whitehead
Institute
for Biomedical Research in Cambridge, Mass.

    Executives of BresaGen Inc., the U.S. unit of an Australian stem cell
company, met with the FDA last spring and learned then that their four
lines of
human embryonic stem cells, all grown atop a layer of mouse cells, would
be
treated as xenotransplant products. "We were a little bit shell-shocked,"
said
Allan Robins, senior vice president and chief scientific officer. "I
think a lot
of companies will see it as a large burden."

    This view is not universal, however, even among scientists who oppose
the
Bush plan.

    Hugh Auchincloss Jr., a surgeon at Harvard Medical School and
chairman of an
FDA committee that reviewed the xenotransplant issue, noted that the FDA
policy,
while stringent, is not an absolute bar to research. Indeed, several
hundred
patients have already participated in various types of xenotransplant
tests,
including the transfer of fetal pig cells into patients' brains in an
attempt to
treat Parkinson's disease.

    Moreover, Auchincloss said, with enough time and lab work, scientists
might
be able to alleviate FDA concerns. He noted that human tests of stem cell
therapies are probably years away, largely because scientists know so
little
about the cells.

    In his speech Aug. 9, Bush said 60 genetically distinct embryonic
stem cell
lines had been derived by laboratories around the world and approved
federal
funding for work only on those cell lines. To reduce incentives for
further
destruction of embryos, he ruled out funding for any cell lines created
after
his speech.

    Because they can be used to grow almost any kind of human tissue,
which
could then be used to repair ailing body parts, the cells offer
considerable,
but unproven, hope for cures. The cell lines were created from
early-stage human
embryos slated for destruction at fertility clinics. Many anti-abortion
activists, one of Bush's most important constituencies, oppose the
research.

    Several scientists have said publicly that they are working on ways
to grow
embryonic stem cells without mixing them with mouse cells. But no
scientist has
publicly claimed to have created an entirely new cell line by such a
method
before Aug. 9.


 PAGE 4
                      The Washington Post, August 24, 2001

    That has led most scientists familiar with the issue to conclude that
all 60
lines were probably created using mouse feeder cells and will have to be
treated
as xenotransplant products.

    "I don't think there's any one of the 60 lines that has not been
derived
using mouse embryonic feeders," said Daley, of the Whitehead Institute.

    However, the possibility cannot be entirely ruled out until the
location and
details of all 60 cell lines have been disclosed.

    The implications of treating most or all of the lines as
xenotransplant
products would be substantial.

    The draft FDA guidelines make clear that labs researching stem cells
will
have to meet special burdens to win approval for any human test involving
xenotransplantation. They will have to perform extensive research and
documentation on their cells that go beyond normal FDA requirements,
including
elaborate study of potential animal viruses. At a minimum, this will
introduce
delay and extra expense.

    Given the complexity of the FDA restrictions, Robins, the BresaGen
scientist, predicted that few companies would plunge into human tests of
stem
cells grown together with mouse cells. He said those will be used for
research
for the next few years, but eventually companies will create new cell
lines
grown only on human feeder cells. They will do so either with private
money or
by overturning the Bush limitations on federal funding, Robins and other
researchers predicted.

    In fact, it appears the FDA restrictions have already set off a
behind-the-scenes race among labs to create -- and patent -- alternative
means
of growing stem cells that don't depend on mouse feeders.

    The only company that has publicly claimed success with a mouse-free
technique is Geron Corp. of Menlo Park, Calif. "We have accomplished it,"
said
David Greenwood, the company's chief financial officer. But he declined
to say
whether Geron had managed to create any new stem cell lines using the
technique
before Aug. 9.

    Several researchers predicted that if stem cells began to show
promise, the
politics would change, and they would win permission to work on new cell
lines
with federal money.

    "If the research looks great and we're ready to go to human trials,
we will
need more stem cells," said Jeffrey Rothstein, a neurologist at Johns
Hopkins
University in Baltimore who works in the field. "We'll turn to the
president or
Congress and get them to do the right thing."

--------------------------------------------
Why not get them to do the "right thing" NOW???
Linda

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