BRAVE NEW CELLS by Christine Gorman Time, May 1, 2000
It's the kind of scene you'd expect in a thriller by Michael Crichton or Robin Cook. A scientist throws
some nondescript cells into a lab dish, leaves them alone for a bit and returns to find a disembodied heart
thumping away.
That's not quite what's happening in Roger Pedersen's lab at the U. of California in San Francisco - at
least not yet. But he has managed to turn a group of carefully tended progenitor cells into a patch of
thriving beating cardiac muscle. "It's amazing," Pedersen says, "when you put unspecialized cells away,
come back after the weekend and there's a clump of heartlike cells beating before your eyes in a dish."
And that's just the beginning. Someday, scientists hope to use cells like these to cure diabetes,
Parkinson's disease and multiple sclerosis,as well as to reverse congestive heart failure and heal spinal-cord
injuries. But there are some aspects of this story that are brave new world-ish. Known scientifically as stem
cells, Pedersen's marvelously pliable cells are derived from seven-day old human embryos, which are
destroyed in the process. Although not all stem cells are produced this way, embryonic stem cells seem for
now to have the greatest potential for medical miracles.
Pedersen- and the handful of other scientists working with human embryonic stem cells- uses embryos
left over from fertility attempts that would otherwise be thrown away. Still, treating human embryos like so
many tissue factories seems straight out of Huxley. It certainly doesn't sit well with antiabortion activistsor, in many cases, with lawmakers. In 1996 Congress banned human-embryo research by federally
supported scientists, forcing researchers like Pedersen to seek private funding (most of which has been
provided by Geron, a Menlo Park, CA, biotech comp.
A lot has changed in the past couple of years, however, that might persuade Congress to reconsider.
Last September the National Bioethics Advisory Commission concluded that harvesting stem cells from
discarded embryos is normally akin to removing organs from dead people for transplant. Also, the National
Institutes of Health has seized on a possible loophole. In their view, federally funded scientists can do
research on stem cells as long as someone else, say in the private sector, actually dismantles the embryos.
Most important, a small but influential group of Republicans and Democrat on Capitol Hill has started
pushing for a relaxation of federal policy.
This week, Senator Alan Spector of PA, who has called stem cells "averitable fountain of youth," will
convene a hearing on Capitol Hill to review both the science and the ethics of the research. "Finally there is
a very possible solution to conquering disease that were always thought to be incurable," says actor
Christopher Reeve, who has been paralyzed since his spinal cord was crushed in a fall from a horse in 1995,
and others, is scheduled to testify,. " This research should go forward as fast as possible," Reeve say. To
that end, Senators Specter, a Republican, and Tom Harkin of Iowa, a Democrat, have introduced a bill to
lift the ban. Just how far they'll get in an election year is anyone's guess.
To critics, anything that requires the destruction of human embryos - no matter what the reason- is
abhorrent. Calling that "worse than abortion," Richard Doerflinger, a director of policy for the National
Conference of Catholic Bishops, says, "If (the embryo) is a member of the human family, you cannot
destroy that being for the sake of others."
The ethical considerations aside, researchers have so far offered promises aplenty about what stem cells
can do but very little proof. Scientists acknowledge that many "nontrivial" technical obstacles remain
to be overcome, and they are worried that stem-cell therapy has been so overhyped that it can't help but
disappoint: There has even been one death from a related treatment.
To complicate matters, adults have stems cells, too. Lurking in the microscopic nooks and crannies of
the brain, bone marrow and other organs, these stem cells live in a state of perpetual readiness. Then
when say, the lining of the intestine becomes worn, the body signals the appropriate stem cells to start a
process called differentiation, in which they divide and give rise to lots of mature, fully functioning intestinal
cells.
These adult stem cells appear to be fairly restricted in what they can become. (Stem cells in the bone
marrow usually give rise to different types of blood cells: stem cells in the muscles generally give rise to
muscle.) Otherwise, Kafkaesque as it may seem, you could wake up one morning to find that your foot has
turned itself into a liver. In any case, while there's no controversy over the use of adult stem cells, their
potential benefit as a therapy seems limited.
Stem cells derived from embryos, on the other hand, can become just about anything-from teeth to
STEM CELLS - Page 2
muscle to neurons. In fact, they're so strongly primed to differentiate that scientists have a tough time
keeping them in their original state. James Thomson of the University of Wisconsin was the first to pull off
the feat in 1998. He now has an entire tissue bank of stem cells that he hopes one day to turn into
specialized tissue almost at will- eliminating the need for fresh embryos.
Stem cells can also be obtained from aborted fetuses in a process developed two years ago by John
Gearhart at the Johns Hopkins School of Medicine in Baltimore. Gearhart harvested cells from the region
that gives rise to the testes or ovaries. Such fetal stem cells appear to be as malleable as embryonic once.
One feature that all stem cells share is an urge to travel. Evan Snyder, a neurobiologist at Harvard
Medical School in Boston, has found that stem cells are attracted to injured tissues, perhaps because of
biological cues released by dying or diseased cells. Indeed, one of Snyder's lab colleagues found that a
batch of stem cells had migrated from one side of a rat's brain to the other to infiltrate a tumor.
Stem cells are also highly responsive to their surroundings. Researchers have taken adult stem cells
from the brains of rats and put them in bone marrow and watched in astonishment, as they spewed out
blood cells. True, they did not form all the different blood-cell types- just a few. But until then no one had
known that adult stem cells could adapt even that much to their environment.
And the extraordinary thing is that it's the specialized cells surrounding them- their older brothers and
sisters if you will- that provide the directions, not in words but in biological signals, like growth factors and
surface proteins and by simply touching them.
David Anderson and his colleagues at Cal Tech have, for example, identified many environmental
triggers that get the nervous system's stem cells to turn into neurons or into their supporting glial cells.
They've also gone inside stem cells to isolate the genes responsible for transformations. As with most adult
stem cells, these cells appear, so far, to be limited in the types of tissue into which they can differentiate.
Yet they still give rise to many different kinds of neurons- from sensory cells in your nose to touch
receptors on your fingertips. The next step, Anderson says, is to figure out how that happens.
Pretty heady stuff, especially for neurologists who have spent most of their professional lives believing
that even if the adult brain had stem cells, they'd never yield new neurons. Now the scientists have at
least two options to consider. They can train stem cells to produce nerve tissue in a petri dish and then
implant the new tissue in an ailing brain. Or, as Fred Gage at the Salk Institute in La Jolla, CA, suggests,
they can tweak the brain's stem cells to start churning out new neurons. If you could do that, Gage says, "it
would take away the controversy over embryonic research." There's much more to learn, of course, and
many pitfalls to avoid. Consider the case of a 52-year-old American athlete with Parkinson's disease, who,
in 1989- before human stem cells had been isolated from the brain- traveled to China for a fetal-cell
transplant. The goal was to replace some of the diseased brain neurons with newly differentiated fetal
nerve tissue. While that approach has been at least partly successful in hundreds of other cases, something
went dreadfully wrong this time. About two years later, the man suddenly developed trouble breathing and
died.
An autopsy uncovered a hard mass of tissue pressing on his brain stem which controls breathing,
among other things. Apparently, the surgeons had scooped up a few extra fetal cells that then migrated &
became cartilage, skin and hair cells.
Clearly, researchers don't know enough to start injecting stem cells into humans anytime soon, despite
predictions that the first human trails could begin in the next couple of years. Just don't expect to hear a lot
about what's going on behind closed lab doors, if the current congressional ban continues and stem-cell
research remains almost entirely in the hands of biotech companies. "That's actually the worst-case
scenario because now the public has no input," says Larry Goldstein, a cell biologist at University of
California at San Diego. "Companies have to be motivated by profit, so they aren't necessarily going to tell
us what they are doing."
With or without federal funding, stem-cell research will continue. Scientists may even sidestep the
abortion issue by figuring out how to make adult cells act more like embryonic ones. But the private sector
isn't going to wait to find out if that's feasible. Tens of thousands of embryos are created in in-vitro
fertilization clinics each year and never implanted. If the Federal Government wants to have a say in how
they get used, it will have to pay for the privilege.
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VIEWPOINT - Christopher Reeve USE THE BODY'S "REPAIR KIT" Time, 5/1/00
We must pursue research on embryonic stem cells. With the Life expectancy of average Americans heading
as high as 75 to 89 years, it is out responsibility to do everything possible to protect the quality of life of the
present and future generations. A critical factor will be what we do with human embryonic stem cells.
These cells have the potential to cure disease and conditions ranging from Parkinson's and multiple
sclerosis to diabetes and heart disease, Alzheimer's, Lou Gehrig's disease, even spinal-cord injuries like my
own. They have been called the body's self-repair kit.
Their extraordinary potential is a recent discovery. And much basic research needs to be done before
they can be sent to the front lines in the battle against disease. But no obstacle should stand in the way of
responsible investigation of their possibilities. To that end, the work should be funded and supervised by
the Federal Government through the National Institutes of Health. That will avoid abuses by for-profit corporations, avoid secrecy and destructive competition between laboratories and ensure the widest possible
dissemination of scientific breakthroughs. Human trials should be conducted either on the NIH campus or in
carefully monitored clinical facilities.
Fortunately, stem cells are readily available and easily harvested. In fertility clinics, women are given a
choice of what to do with unused fertilized embryos: they can be discarded, donated to research or frozen
for future use. Under NIH supervision, scientists should be allowed to take cells only from women who
freely consent to their use for research. This process would not be open ended; within one or two years a
sufficient number could be gathered and made available to investigators. For those reasons, the ban on
federally funded human embryonic stem-cell research should be mifted as quickly as possible.
But why has the use if discarded embryos for research suddenly become such an issue? Is it more
ethical for a woman to donate unused embryos that will never become human beings, or to let them be
tossed away as so much garbage when they could help save thousands of lives?
Treatments with stem cells has already begun. They have been taken from umbilical cords and become
healthy red cells used as a potential cure for sickle-cell anemia. Stem-cell therapy is also being used against
certain types of cancer. But those are cells that have significantly differentiated; that is, they are no longer
pluripotent, or capable of transforming into other cell types. For the true biological miracles that researchers have only begun to foresee, medical science must turn to undifferentiated stem cells. We need to
clear the path for them as rapidly as possible.
Controversy over the treatment of certain disease is nothing new in this country; witness the
overwhelming opposition to government funding of AIDS research in the early '80s. For years the issue was
a political foot-ball until a massive grass-root effort forced legislators to respond. Today, the NIH is
authorized to spend approximately $1.8 billion annually on new protocols, and the virus is largely under
control in the US.
While we prolong the stem-cell debate, millions continue to suffer. It is time to harness the power of
government and go forward.
WHAT THE CELLS ARE AND WHY THEY'RE CONTROVERSIAL- unspecialized stem cells taken from in-vitro
fertilized embryos that are less than a week old. The cells can give rise to many types of tissue, including
brain, muscle, nerve & blood.
1. FERTILIZATION - egg and sperm united to form an embryo in petri dish
2. 1 TO 5 DAYS - the embryo divides again and again and takes shape as a sphere called a blastocyst
3. 5 TO 7 DAYS - Embryonic stem cells are removed from the inner cell mass
4. STEM CELLS - Once the cells have been removed, the embryo can no longer survive to become a fetus
5. SPECIALIZATION - Stem cells are grown in cultures that direct their differentiation into more advanced
tissues