The Philadelphia Inquirer
Monday, July 16, 2001
Stem-cell research provides scientists with new hope
By Faye Flam
INQUIRER STAFF WRITER
Second of two articles

As President Bush agonizes over whether to allow taxpayer-funded
research on stem cells from human embryos, neurologist Jeffrey
Rothstein is injecting these cells into mice to see whether they can
slow the relentless nerve degeneration that comes with amyotrophic
lateral sclerosis, or Lou Gehrig's disease.

Rothstein and his colleagues at Johns Hopkins University,
who are privately funded, are transplanting so-called embryonic
stem cells into mice with a condition similar to ALS, which often
starts with weakness in the arms or legs and eventually robs the
patient of the ability to walk, talk, and, in the end, breathe.

Other scientists around the country, most of them testing the
controversial embryonic cells in mice or rats, are looking at their
potential for some of the most devastating conditions - brain
diseases such as Parkinson's and Alzheimer's, spinal-cord injuries,
and the irreparable scarring caused by heart attacks.

The research is so new and the power of these cells is so little
understood that scientists don't know whether stem cells will
revolutionize medicine. But they will never know if they aren't
allowed to study them, they argue.

Adding fuel to the debate over using embryos is new evidence
that stem cells taken from adult donors show some of the same
promise.

Currently, research is allowed on embryo stem cells only if private
money is used, but that restriction has made such research
impossible for many scientists, who can't gather sufficient funds.
Wise Young, director of the W.M. Keck Center for Collaborative
Neuroscience at Rutgers University in Piscataway, Middlesex
County, said stem cells represent one of the most promising
avenues of research for spinal-cord injury. If Bush decided
to allow federal funding for work with these cells, "that would
stimulate a flurry of research in my lab and other labs."

"Stem cells are a very major issue to the spinal-cord injury
community," Young said. "Why should they be penalized for
the religious beliefs of a few?"

The promise of these embryonic stem cells comes from their
seemingly magical ability to transform themselves into any
of the more than 100 kinds of tissue that make up the human
body.

First isolated and grown in the lab in 1998, the cells have spawned
visions of new spinal-cord tissue for paralysis patients, pancreatic
cells to cure diabetes, heart cells that would repair the scarring
of a heart attack, reinforced bone for osteoporosis, or new skin
for burn victims.

Currently, some embryonic stem cells are taken from aborted
fetuses, isolated, and then allowed to multiply in culture dishes.
Others come from the microscopic embryos that are routinely
created and either frozen or destroyed in fertility clinics. Such
embryos develop for just a handful of days and, never progressing
beyond the stage of a cluster of "undifferentiated" cells, have yet
to specialize as different types of tissues.

Lobbying against using embryonic stem cells are the Catholic
Church and others who believe that life begins at conception
with a fertilized egg.

These groups argue that there is no need to exploit human
embryos, citing reports of stem cells being obtained from bone
marrow and other sources in adults, either live donors
or cadavers.

Scientists are not yet ready to say whether adult cells would
work as well as embryonic cells. Not enough research has
been done, they say, and almost all of it has been in animals.

So far, embryonic stem cells have been turned into more than
100 different types of cells, far more than adult stem cells.
Also, embryonic stem cells can reproduce indefinitely in the
lab; adult stem cells eventually die.

Peter Donovan, who conducts stem-cell research at Thomas
Jefferson University Hospital, said it is possible that the
medical community may decide never to use embryonic
stem cells, opting instead for the adult cells. But to learn
how to use any of these stem cells, he said, "we'll need
to study both types."

John McDonald at Washington University, St. Louis, has
been studying the embryonic stem cells as a treatment for
paralysis. In 1999, he injected the severed spinal cords
of paralyzed rats with rat stem cells.

While the rats didn't recover completely, they gained
function - some degree of mobility, sensitivity, bladder
control - the kinds of things that can be important to
people with spinal-cord injuries. And such success may
not ever come from the adult stem cells, he argued.

He has since begun using human embryonic stem cells in
rats and mice, with similar results.

McDonald just started testing this technique, using stem
cells from pig embryos, on people paralyzed by spinal-cord
injuries. There are no results yet from the one patient who
as received treatment.

Meanwhile, Ira Black of the New Jersey College of Medicine
and Dentistry, working with former Hahnemann University
professor Darwin Prockop, who is now at Tulane in New
Orleans, is concentrating on adult stem cells. They obtained
such cells from bone marrow taken from student volunteers.

Black and Prockop knew that stem cells from bone marrow
could become bone, cartilage, fat and muscle. But last year
they proved they could also transform it into brain tissue.
That led them to inject the stem cells into rats that had been
given a form of Parkinson's disease. The cells took up
residence in the brain, where new brain tissue was needed,
Prockop said, and the animals showed some improvement.

Prockop said the bone marrow stem cells are now being
tested as a treatment for a genetic abnormality called brittle
bone disease, which causes people to fracture at the slightest
impact. In animals, the cells seem to migrate to the deficient
skeleton. Human trials are expected soon.

Some opponents of embryo research point out that some
patients are now getting stem cells from umbilical-cord blood,
taken when babies are born. But so far such cells have only
produced blood cells, limiting their use to blood diseases
such as leukemia.

The first study to compare the benefits of embryonic stem
cells with adult cells is the ALS work on mice being done
at Johns Hopkins.

Early results, in which they transferred mouse stem cells
to mice, showed "dramatic" improvement for the mice that
got embryonic stem cells, Rothstein said, but not for the
ones that got cells from other sources. The Hopkins group
has since begun transplanting human stem cells of different
types into the mice. The results, Rothstein said, are
confidential, having been sent to a journal but not yet
published.

Rothstein hopes the mice experiments will answer some
questions beyond ALS.

"We're one small disease, but it has a pretty big impact,"
said Rothstein. Their research could point to similar treatments
for multiple sclerosis, Parkinson's disease, paralysis,
or Alzheimer's.

Even if the adult stem cells prove superior in the ALS trial,
Rothstein remains convinced that embryonic stem cells
hold tremendous promise. He said that any decision
to continue the federal funding ban would be
"a bad mistake."

Donovan of Jefferson argues that embryonic cells hold
keys to our understanding of the way life works.
Virtually every cell in the body carries the person's complete
genetic code, and yet the cells take myriad forms and functions.
Some mysterious mechanism seems to tell them whether
to become bone, muscle, organ, nerves, or blood.

Stem cells may hold the secret behind the cells' ability
to find their identities, and, combined with the knowledge
from the human genome project, could give scientists
a huge insight into the way life is put together.

Such an understanding would be critical, Donovan said,
for making the stem cells truly useful in medicine.

Still, he cautioned that impressive new ideas - such as gene
therapy - don't always live up to the public's hopes.

"We don't want to promise too much too soon."

Faye Flam's e-mail address is [log in to unmask]

SOURCE: The Philadelphia Inquirer
http://inq.philly.com/content/inquirer/2001/07/16/front_page/STEMSCI16.htm?template=aprint.htm

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