While politicians debate the ethics of embryonic stem cell research,

[Max]

While politicians debate the ethics of embryonic stem cell research,
scientists at UW and elsewhere push the envelope with more breakthroughs
By MARILYNN MARCHIONE
of the Journal Sentinel staff
Last Updated: July 29, 2001
Medical Science


Photo/Jeff Miller, UW-Madison
Great promise, great concern: Culture trays containing human embryonic stem
cells are studied in developmental biologist James Thomson's research lab.

Photo/Jeff Miller, UW-Madison
All-purpose cells: Microscopic views show human embryonic stem cell colonies
in different stages of development. The stem cells sometimes include a core
of undifferentiated cells surrounded by a margin of differentiated cells,
such as the small colony at right in Figure B.

The Stem Cell Process


Related Coverage

Funding ban: Complicates life for researchers
Delegation: Divided on stem cell research


Quotable

The decision will be made. I doubt it will be quickly. . . . We've
committed to continuing regardless of what the decision is.

- James Thomson,
stem cell discoverer

Coming Monday

The state's biotechnology industry is working harder than ever - not just in
the labs, but also in the political arena, where it hopes to head off
restrictions on research.

Madison - While politicians debate whether to let tax money be used for
embryonic stem cell research, scientists are advancing it in ways that
significantly raise the stakes.

"We're not waiting," said the cells' discoverer, James Thomson of the
University of Wisconsin-Madison.

Thomson has quietly started from scratch to grow new embryonic stem cells -
the body's most primitive and universal building blocks - that would comply
with existing federal funding rules in case President Bush lets them stand.
None of the current cells would qualify.

Another UW scientist has taken Thomson's cells and grown blood "master
cells" from them - an extraordinary, soon-to-be-published feat that some
experts say might one day provide a cure for leukemias and other cancers as
well as safer blood for transfusions, free of health threats such as viruses
and mad cow disease.

A third UW researcher has grown clumps of human nerve cells, a hoped-for
treatment for spinal cord injuries and neurological diseases, and a fourth
just made a key discovery toward growing cells that would make insulin, a
potential treatment or cure for diabetes. Both just submitted their work to
medical journals.

Meanwhile, at Johns Hopkins University in Baltimore, researchers led by John
Gearhart are helping paralyzed mice walk by giving them primitive, stemlike
cells from aborted human fetuses. Fetal cell research has long been eligible
for federal funding; abortion opponents have been unable to block that work.

In the private business world, scientists recently announced some very
controversial experiments: A Virginia infertility clinic made embryos just
to do medical research on them, and a Massachusetts firm started trying to
clone embryos to collect their stem cells.

In some respects, the science is advancing at a dizzying pace. In others, it
is moving agonizingly slowly, hurt by a lack of resources.

"There are a lot of things we'd like to do but can't," said Jon Odorico, an
assistant professor of surgery at UW who is working on the insulin-producing
pancreatic cells.

Only two applications were received by the March 15 deadline that the
National Institutes of Health had set for the first round of grants for
embryonic stem cell research, a process Bush stopped until he decides
whether the work should be publicly funded at all.

"The decision will be made," Thomson said. "I doubt it will be quickly. It
could be tomorrow or it could be six months from now. We've committed to
continuing regardless of what the decision is."

Bush's decision will be one step in a long process, Thomson noted. Congress
may intervene, and lawsuits inevitably will be filed by whatever side loses.
Two suits already have been filed, one by Thomson and other researchers. The
final word may be years away.

In Thomson's view, stem cells represent the discovery of a lifetime. He
compares it with polymerase chain reaction or PCR, a way to amplify DNA that
made genetic research possible and affected everything from crime
investigations to testing for diseases.

"PCR revolutionized biology, and embryonic stem cells are going to do the
same thing," Thomson said. "They're going to be used for a whole host of
things we can't predict right now."

The scientific community stands solidly behind him on that point. In
February, 80 Nobel Prize winners wrote a letter urging federal funding. The
heads of dozens of universities and academic medical research centers did
the same, and a recent report by NIH scientists concluded that embryonic
stem cells have unique potential for treating diseases and unraveling basic
biological mysteries.

But anti-abortion activists, Roman Catholics and many others oppose the
research because an embryo must be destroyed to get the stem cells.

Between the proponents and opponents are people who hope that some
compromise can be found to allow promising areas of science to move forward
in a limited and ethically controlled way.

In the meantime, without federal funds for their work, Thomson and about a
dozen others at UW are continuing embryonic stem cell research at two
privately funded labs with money from the Wisconsin Alumni Research
Foundation, other foundations, biotech firms, disease advocacy groups and
drug companies.

Blood 'master cells'
The most stunning recent development has been UW scientist Dan Kaufman's
work to grow from Thomson's embryonic cells hundreds of colonies of blood
"master cells," which then formed red blood cells, clotting factors called
platelets and other blood cell types.

Isolating the blood master cell, called the adult hematopoietic stem cell,
and getting it to grow and multiply in a lab dish has been the ultimate
quest in hematology, said Richard Aster, a Medical College of Wisconsin
professor and former president of the Blood Center of Southeastern Wisconsin
who's nationally known for his pioneering work on platelets.

"It's something people have been trying to do for a long, long time, the
Holy Grail in this kind of work," he said.

The hematopoietic stem cell is what's actually being given when patients
have bone marrow transplants to try to cure cancer or replenish immune
systems destroyed by cancer treatment.

But scientists have never been able to isolate that cell from marrow or
circulating blood. Because they can't, when they do a transplant, they
remove all of a donor's white blood cells, knowing that the stem cells are
somewhere in the mix.

"There are very few of them, to be sure, maybe one in 1,000 (cells) at
best," Aster said.

That leads to the second problem - trying to multiply those scarce adult
stem cells into enough to treat a cancer patient. Even when researchers
establish colonies containing such cells, it's not possible to expand them
without the cells losing their "stemness."

"They immediately differentiate. It's like trying to catch a greased pig.
They won't sit still," Aster said.

If Kaufman has gotten blood master cells from embryonic stem cells and
multiplied them in the lab, "that would remove a huge obstacle" to treating
diseases, especially for the three out of four people who can't have marrow
transplants because they lack a matched donor, Aster said.

"That's exciting if that's true," he said of what Kaufman reportedly has
achieved.

Blood grown from embryonic stem cells could have other big uses.

"This could potentially be used to make cells that could be transfused, and
you would not have to worry about viruses," Kaufman said. "Theoretically,
there is no limit to the number of cells you could produce."

Aster doubted that Kaufman's work would replace donated blood for
transfusions, saying the growth factors and culture media needed to make the
blood cells are so expensive that it probably wouldn't be worth it except
for rare blood types.

"This isn't going to happen for another hundred years, that people would
actually make blood for transfusions that way," Aster said.

Thomson disagreed.

"Just because the growth factors now cost $200 for a tiny vial doesn't mean
they always will," he said, pointing out past examples where such things
became cheaper once they were commercialized and mass-produced in industrial
settings.

Other research
Other promising work is being done by Su Chun Zhang, a UW scientist who has
taken Thomson's embryonic stem cells and grown them into colonies of neural
cells. He can't direct the cells to form specific nerves yet but is working
on that next, Thomson said.

Odorico, an assistant professor of surgery, has a $500,000 grant from the
Juvenile Diabetes Research Foundation to try to grow the kind of pancreatic
cells that are damaged by diabetes. He started that work in January and
recently made a key discovery on the genetics of how embryonic stem cells
can be made to turn into cells that produce insulin.

All this work involves differentiation, or getting the embryonic stem cells
to turn into specific kinds of cells and tissues. Thomson is involved in
remaking the embryonic cells themselves.

When he first isolated such cells in 1998, it was before the NIH published
rules for funding such research. His cells now conflict with the rules on
two points. The first is a wording issue with the embryo donation consent
form that is more style than substance but still an obstacle.

The bigger problem is that the NIH rules say the cells have to have been
derived from frozen embryos. Thomson used fresh and frozen. Ironically, the
very steps he used to ensure the anonymity of the embryos he was working
with now prevent him from separating donated embryos that came from Israel,
which were frozen, from those that came from the UW infertility clinic,
which were a mix of fresh and frozen.

"I have in my notebook I got five embryos today," but not which came from
where, he said. "We pretty much do know which ones are fresh (and which are)
frozen, but we can't document it in a satisfactory way."

So he started over last fall. The new consent forms and experimental
procedures were just approved by the UW committee that oversees human
research.

"If we got the appropriate (embryo) donations today, it would take six
months" to establish a self-perpetuating colony of stem cells, Thomson said.

"What I'm worried about is Washington will change (the rules) and our new
cell lines won't qualify," he confessed.

That would send him back to the lab, to start all over yet again.

Appeared in the Milwaukee Journal Sentinel on July 29, 2001.


__________________________________________________ __
Maksim (Max) Bily
mail to : imax@odyssee.net
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