Viability Of Stem Cell Plan Doubted
Bush Policy Could Limit Research, Scientists Say
By Ceci Connolly, Justin Gillis and Rick Weiss
Washington Post Staff Writers
Monday, August 20, 2001; Page A01

Mounting uncertainties about the quantity and quality of
embryonic stem cells available for research under a new
Bush administration policy have persuaded many biologists
that the president's approach poses serious constraints for
the development of new medical treatments for diseases
such as Parkinson's, diabetes and stroke.

Skepticism among those scientists focuses on the existing
stocks of stem cells available for research. Under Bush's
guidelines, federal dollars may be used to study the versatile
and medically promising cells only if they came from donated
fertility clinic embryos that were already destroyed by Aug. 9.

Bush said at least 60 self-replenishing colonies, or "lines,"
of such cells existed by that date, a number four times greater
than many scientists were aware of. But the National Institutes
of Health has yet to produce information about the lines or
their producers, feeding speculation that many of those 60
do not exist, are of poor quality or are under such tight
commercial control as to make them unattractive to researchers
hoping to study and perhaps profit from them.

NIH officials have asked scientists to be patient, reassuring
them that plenty of cells are available and promising that
details will soon be forthcoming. But contrary to predictions
made by top government officials, only a few companies or
laboratories have emerged after Bush's announcement to say
publicly that they, too, have eligible cell lines.

And new questions have begun to arise about the adequacy
of the consent processes used to obtain the cells and the
racial diversity of the available cells -- a factor that could
ultimately affect the availability of stem cell-based therapies
for some minorities.

The number and variety of cell lines available is important
because stem cells are highly finicky and quite volatile.
Cell lines can "crash" -- or die -- at any moment, or they can
spontaneously turn into specialized cells, rendering them
useless for later work. In addition, there are subtle genetic
differences between each cell line, differences that can
affect their behavior and utility in research.

To limit researchers to 60 cell lines, critics say, is like telling
mathematicians they can pursue their studies but they can
never use numbers bigger than 10.

"I think it's a ridiculous policy," said George Daley,
a leading stem cell researcher at the Whitehead Institute
for Biomedical Research in Cambridge, Mass. Evan Snyder,
another stem cell expert at the Harvard Medical School,
called Bush's approach "scientifically naive."

NIH Seeks Cooperation
The NIH has not yet produced any information on the
condition of the 60 cell lines, a critical issue for scientists
aiming to work with them. And the agency appears to
have only sketchy information on whether the cell lines
were created after receiving proper consent from the
embryos' donors, a fundamental criterion laid down
by the president.

NIH administrators say the Bush policy is workable,
and they are scrambling to answer growing doubts.
They have summoned top executives and scientists
from about nine stem cell laboratories around the world
to attend meetings at the NIH's Bethesda campus this
week to gather information and seek pledges of cooperation.

Bush administration lawyers are negotiating an initial
agreement to give government scientists access to some
of the most important cell lines. They hope that agreement
will become a model for universities around the world.

Lana Skirboll, director of science policy at the agency,
said NIH aims to release more detailed information on the
cell lines in coming weeks. "Our goal, our single goal,
is to get these cells to the investigator community,"
she said.

Still, it is clear the Bush administration will have to work
hard to reassure the scientific community of its approach.
On Friday, the world's largest scientific body, the American
Association for the Advancement of Science, called on the
White House to give immediate access to the list of 60
cell lines as well as details of how the White House
policy will work.

Research on human embryonic stem cells is one of the
most promising, but controversial, fields of modern
biology. The cells are usually derived from microscopic,
days-old embryos that are due to be discarded at fertility
clinics. The value of the cells is their flexibility -- they
have the ability to become any of the more than 200
specialized cell types in the human body, offering a
potentially unlimited source of new tissues for ailing
patients.

But because an embryo is destroyed to extract the cells,
many people oppose the research for moral reasons,
arguing that the embryo is a form of human life.

Since 1996, federal law has prohibited the use of tax dollars
to destroy human embryos. The Clinton administration,
however, adopted rules saying federally funded scientists
could conduct experiments on stem cell lines as long as
they did not themselves participate in embryo destruction.
Cells were to be derived from embryos destroyed with
private money in private labs, then shipped to federally
funded scientists for study.

The government was on the verge of issuing its first
stem cell grants when Bill Clinton left office. Bush's new
policy seemed to be an artful compromise between the
Clinton plan and conservatives' calls to ban the research
altogether. Bush's plan will permit federal funding on
stem cell lines created before his speech Aug. 9, but
prohibit funding for any that might be created later.

Search for Cell Lines
The policy was predicated on the existence of 60
genetically distinct lines of stem cells, which the
administration said would supply enough diversity
to allow scientists to undertake serious work on new
treatments.

But the number 60, based on a relatively hasty NIH
telephone survey, came as a shock to virtually every
scientist working in the field. Fewer than a dozen cell
lines have been identified in scientific literature.

Andy Cohn, spokesman for a University of Wisconsin
foundation, watched the Bush speech with James Thomson,
the scientist who in 1998 first isolated human embryonic
stem cells. When Bush made the claim about 60 cell lines,
"we both almost fell off our chairs," Cohn said.

Since then, counting by news organizations, including
The Washington Post, has turned up new cell lines,
mostly in laboratories already known to be working
in the field. But none of those counts has produced
more than 23 lines.

Requests from lawmakers and news organizations that
the White House document its claim of 60 cell lines have
gone unanswered. "The burden of proof is on anyone
who doubts" the claim, White House spokesman
Ari Fleischer said.

The debate over the number is more central than it might
seem at first, for several reasons. For one, a larger number
of cell lines would be insurance against the risk that
some of the existing cell lines prove unusable.

Secondly, there is the issue of genetic diversity. Scientists
envision using stem cells to create more specialized cells,
such as those of the heart, liver or brain. Those would be
implanted into ailing patients to restore organ function.
Much as with a liver or heart transplant, it may prove critical
to find a good immunological match between the implanted
cells and the recipient to try to stave off rejection.

Such matching is easier within racial and ethnic groups
that are more closely related. The NIH has not obtained
information about the ethnic origin of the 60 cell lines.
Many of the ones that have come to light in recent days
were created in Asia, which might limit their usefulness
in treating people of European or African ancestry.
"Ours would come from people of Chinese-Asian
background," said Robert Klupacs, chief executive
of a Singapore company, ES Cell International Pte Ltd.,
that controls six stem cell lines -- 10 percent of the total
cited by Bush.

Standards of Consent
Researchers have also grown worried about whether
the stem cell laboratories obtained adequate consent
from the embryos' donors. In their phone survey, NIH
officials were assured some type of informed consent
had been secured on each of the existing lines. They
asked for copies of the forms, but did not study their
adequacy.

"We didn't analyze the informed-consent forms,"
Skirboll said. "We received them to make sure there
was informed consent. These people who provided
us informed consent, they were held to whatever standard
was in place for the country, the hospital or the facility
they were working in."

That could leave scientists running afoul of the ethics
committees at their universities or research institutions,
which in this country typically demand strict standards
of consent before approving research proposals.

"Too often we have learned that procedures used in
other parts of the world in research with human subjects
do not measure up to the ethical standards we embrace
in this country," according to AAAS, the scientists'
federation.

If some of the consent forms are inadequate, American
researchers would be left with an even smaller pool of
cell lines.

Another unresolved issue is the degree to which
American academic researchers will have access
to the 60 cell lines covered by the Bush policy.
They are controlled by a few companies and laboratories
around the world. Those labs have been filing patent
applications on aspects of stem cell technology, and the
pending applications are believed to number in the dozens.

Researchers may get ready access to the cells, but on the
terms of the labs that created them -- namely, that those
labs retain potentially lucrative commercial rights to future
discoveries. This is likely to be unacceptable to many
universities, which hope to profit from fresh discoveries
their scientists make.

NIH lawyers are negotiating a master agreement with
the Wisconsin Alumni Research Foundation to give
government scientists access to five cell lines it controls.
The agency hopes that agreement will serve as a "gold
standard," a model that universities could use to cut
deals of their own with the cells' owners.

But each university will be responsible for making its
own deals with the labs and companies that control
cell lines, and the Bush policy could make that more
complicated. Because no new cell lines will be eligible
for federal funds, the owners of old lines are likely to
have more leverage in their dealings with scientists
who want to undertake such work. Most people in the
field express optimism that the patent difficulties can
be worked out, but they acknowledge it will be tricky.

"These are not our cells," Skirboll said, so the NIH
can only do so much to make them available.
Nonetheless, she said, the owners "have told us
they have an interest in making these cells available
to scientists."

Antiabortion groups are divided over the Bush
compromise, and although many have accepted
his policy as the best they can get, others have
said they will urge Congress to pass a complete
ban on federal funding.

Advocates of the research regard the new policy
as imperfect, but they also see it as a foot in the door,
a chance to expand the work using millions of federal
dollars. They have therefore made a tactical decision
not to fight the administration. Many hope to increase
the number of cell lines scientists can use,
but incrementally, rather than by going to war again
with antiabortion groups, one of Bush's most
important constituencies.

"Does anybody believe that if the University of
Edinburgh came up with a 61st cell line that can cure
Parkinson's or Alzheimer's, that number of 60 would
not expand?" asked a top biotechnology strategist
who spoke on condition of anonymity. "In the long run,
this number of 60 will be a forgotten relic of the political
debate. The important thing is not so much the number 60.
It's really that the green light went on for federal funding
of this research."

This strategist said the groups with which he is allied
have made a conscious decision to back off, give Bush
some breathing room and let the controversy die down.

"He had a particularly difficult political situation and
he came out the right way," the strategist said.
"I don't think there's any instinct to punish him for that.
This took a bit of political courage."

SOURCE:  The Washington Post
http://www.washingtonpost.com/wp-dyn/articles/A33338-2001Aug19.html

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