Scientists used to think that such potential for cellular
            regeneration was present only in embryos -- that, for
example,
            humans had made their lifetime supply of brain cells by
age 17.
            But that canon is steadily eroding. In the early 1990s,
researchers
            isolated human blood stem cells from adults. And earlier
this month,
            researchers at Osiris Therapeutics Inc. in Baltimore found
a stem
            cell in adult bone marrow that is capable of becoming
bone,
            cartilage or fat. Researchers also believe they may be
close to
            identifying stem cells in the liver, brain and pancreas.
            They're Everywhere
            "I think we will find these stem cells in any organ that
we look,"
            says Harvard Medical School researcher Evan Y. Snyder, who
has
            already isolated brain stem cells from a human fetus and
believes it
            won't be long before someone finds them in adult humans.
"I think
            that when nature develops a strategy for development and a
strategy
            for self-repair, it doesn't make it up each time for every
organ."
            Some scientists remain skeptical that stem cells will be
found in
            every organ. And hunting is a laborious process. Brain
stem cells
            were found in animals a decade ago, but scientists are
still working
            to find them in humans. But if and when they are found,
precursor
            cells would circumvent the ethical and legal problems of
working
            with embryonic stem cells taken from aborted fetuses.
            Douglas A. Melton, chairman of the department of molecular
and cell
            biology at Harvard University, has found promising results
in mouse
            and frog stem cells but hasn't been able to obtain human
embryonic
            cells to apply the work to humans.
            The National Institutes of Health has said it will permit
federally
            funded researchers to use stem cells as long as they don't
actually
            handle aborted fetuses, but the cells won't be available
until
            formal guidelines for their use have been published.
Meanwhile, work
            with the stem cells found in adults is moving along
rapidly.
            In early clinical trials in the area of AIDS, Novartis AG
is
            purifying blood stem cells from HIV patients' own blood,
altering
            them by inserting anti-HIV genes and then reinjecting them
in the
            patients. "We expect the modified stem cells will give
rise to
            progeny cells that are HIV-resistant," says Carol
Grundfest, a
            Novartis spokeswoman.
            Cytotherapeutics Inc., of Lincoln, R.I., is looking for
stem cells
            in the liver, the pancreas and the brain. It reasons that
a single
            type of stem cell may prove useful against many
conditions -- a
            brain precursor cell, for example, could be used against
            Parkinson's, Alzheimer's and other degenerative brain
diseases.
            "The best concept is a drug-in-a-bottle concept -- a cell
product
            that is not patient-specific that could be used to treat a
wide
            spectrum of diseases," says the company's chief executive,
Richard
            Rose.
            Developing Substances
            Some companies aren't waiting for specific types of
precursor cells
            to be discovered. Instead, acting on the belief that such
cells do
            exist in certain body areas, they are developing
substances that can
            activate them.
            One such company is Creative BioMolecules Inc. of
Hopkinton, Mass.
            Its drug, osteogenic protein, is now being implanted in
broken legs
            that have been slow to heal in clinical trials, and the
company says
            results are promising. It believes the drug works by
spurring bone
            stem cells to create new bone, says in-house scientist
Marc
Charette.
            "The body has a large amount of stem cells, and what you
really need
            is the signals to cause them to differentiate," he says.
            If the Food and Drug Administration approves the company's
drug, it
            will be sold by partner Stryker Corp., of Kalamazoo, Mich.
            Biogen is hoping it has found a chemical signal that
causes brain
            stem cells to become the type of cells that produce the
            neurotransmitter dopamine. Those cells are damaged in
people with
            Parkinson's disease, causing its sufferers to have
difficulty moving
            and talking. In a collaboration with Ontogeny, Biogen is
injecting
            rats with a type of protein known as a "hedgehog," which
has been
            shown to play a key role in fetal development.
            To simulate Parkinson's disease, the rats are injected
with a toxic
            chemical. Normally, the toxin shuts down the animal's fine
motor
            control and causes the rat to spin uncontrollably, like a
top. But
            the company found that rats given brain injections of the
hedgehog
            protein in addition to the toxic injection got a much less
severe
            case of the spins, says Joseph M. Davie, the company's
senior vice
            president of research
            At the very least, says Dr. Davie, the hedgehog protein
appears to
            be protecting the brain from the toxin. At best, hedgehog
may
            actually direct stem cells in the brain to create new
nerve cells to
            replace those destroyed. In a separate project, Ontogeny
is hoping
            to generate a therapy that would cause pancreatic tissue
to
            regenerate itself, restoring insulin-making capability and
freeing
            diabetics from daily injections.
            The first step, which the company is now working on, is to
find the
            chemical signals -- generally proteins -- that tell a
developing
            embryo to make a pancreas in the first place. If they can
be found,
            they could be injected into the pancreas in order to spur
stem cells
            to turn into insulin-producing cells.

Margaret Tuchman
Princeton, NJ
B1941/Dx1980
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