By Rick Weiss
Washington Post Staff Writer
Monday, April 24, 2000; Page A11
Five years ago, the prospect of turning a muscle cell into a blood cell, or a blood cell into a liver cell, seemed about as likely as turning lead into gold. Remarkably, however, more and more scientists today are performing these and other feats of biomedical alchemy.
The new work is overturning long-standing axioms of cell biology and intensifying a rancorous national debate over federal funding of human embryo research.
Researchers, politicians, theologians and others are struggling to find a balance between their desire to reap the medical benefits of human embryonic "stem cells"--recently discovered cells whose regenerative powers may prove curative for many diseases--and their discomfort with the fact that human embryos must be destroyed to retrieve those versatile cells.
But adult cells may not always be the crusty, narrow-minded entities that scientists have long presumed them to be, and in fact they may retain some embryonic potential to turn into whatever kind of cell or tissue the body needs. If that's the case, then the need to conduct experiments on human embryos and fetuses may be less than scientists have thought.
In fact, some scientists are coming to suspect that each person harbors all the cells he or she will ever need to regrow or rejuvenate ailing body parts.
"It seems like there is a really good alternative here that is noncontroversial," said David Prentice, a cell biologist at Indiana State University in Terre Haute who studies the molecular signals that tell cells what to be. "We really ought to be investing in this more thoroughly, and people need to be more aware of this alternative."
Two recent advances have suggested that large-scale tissue regeneration may be possible without embryo cells. One is the recent recognition that even adults harbor tiny pockets of stem cells in various parts of their bodies. These relatively unspecialized "adult stem cells" are probably unable to turn into every kind of tissue, as embryonic stem cells can, but they can give rise to certain classes of tissue.
For example, scientists have isolated neural stem cells from adult brains, which can turn into all the kinds of cells normally found in the brain. And last April a Baltimore team reported it had discovered cells known as human mesenchymal stem cells, which reside in bone marrow and can give rise to bone, cartilage, muscle, ligament, tendon and fat tissue.
A second and more unexpected recent discovery was that even some mature, highly specialized cells in adults can enjoy midlife career changes--a finding that defies a basic tenet of mammalian development.
During the nine months of human fetal development, countless "undifferentiated" cells that initially had the potential to become any body part gradually settle into one or another of the body's bureaucratic niches as liver, bone, nerve or other cells. Scientists have long believed that those decisions were permanent.
Then came Dolly the sheep, cloned from a single adult udder cell that was transformed into an embryo cell. Dolly offered bleating evidence that even a grown-up cell can sometimes start over again.
Now scientists are finding other instances in which mature cells can be coaxed into youthful "pluripotency," the term they use to indicate a cell's potential to become many things.
In December, Kathyjo Ann Jackson and colleagues at Baylor College of Medicine in Houston reported the surprising discovery that mouse skeletal muscle cells could give rise to blood cells. In January, a team of Canadian and Italian researchers reported it had taken from a mouse's brain a few "neuronal stem cells," which had been thought capable only of giving rise to other nervous system cells. When the nerve precursor cells were transplanted into the bone marrow of other mice, they gave rise not to nerve cells but to blood cells.
That transition from brain to blood was more shocking than the Baylor transition from muscle to blood. Muscle cells and blood cells are closely related (both develop from the same kind of precursor cell during fetal development). But brain cells and blood cells have quite separate roots. The work suggests that human neural stem cells could have therapeutic potential for diseases unrelated to the nervous system.
Other scientists reported a similarly astonishing leap of lineages last spring, when they showed that blood-related cells taken from a rat's bone marrow could give rise to liver cells. Scientists were dumbfounded by the news because, as with brains, livers normally arise from a line of cells completely separate from those that make blood.
Findings such as these offer tantalizing evidence that scientists someday may be able to grow any tissue they want from a person's own cells, without having to rely on embryonic and fetal tissues. But as exciting as that prospect is, many researchers warn against cutting off embryo and fetal research before finding out which cells offer the most medical potential.
For one thing, some scientists remain skeptical that mature, specialized adult cells can really change so radically as they seem to have done in the recent experiments. The work has not been replicated by others, and perhaps some of these remarkable transformations were the result of contamination with a few stem cells or blood or liver cells in the starting samples.
Even if adult cells can be made to turn into other kinds of cells that the body needs, some experts say they would be worried about using those adult cells because they will almost certainly contain a lifetime's accumulation of mutations and other kinds of damage. That is, the "new" tissue those adult cells make could be genetically old, while tissues grown from embryonic and fetal cells would be, genetically speaking, in mint condition.
Finally, researchers note that work on embryonic and fetal stem cells is much more advanced than work on adult cells, with some predicting clinical trials for patients with the nervous system disorders Lou Gehrig's disease and Parkinson's disease within the next year or so. Those studies will offer crucial information about the potential of stem cell therapies generally, and they should not be abandoned, supporters say.
"In general, I think we don't know enough about the potential of any of these cells to say that one has greater potential than another," said Fred Gage, a stem cell researcher at the Salk Institute in La Jolla, Calif., echoing a common refrain from stem cell scientists.
"My bottom line is we should not be making policy decisions about which
cells are best, or which kind of research to support, because we don't
have enough data to make that decision," Gage said. "It could be such a
mistake to limit our inquiries to just one kind of cell."