NEUROSCIENCE is coming of age. For the first time there is a realistic hope
of designing treatments for paralysis, head injuries and stroke, and progressive
neurological diseases such as multiple sclerosis and brain cancer.
But just as scientists pick up speed in their quest for new therapies,
politicians are applying the brakes. The British Parliament recently voted down
proposals to allow researchers to study stem cells harvested from
embryos—cells that may ultimately help paralysed people walk again and
treat devastating neurological diseases. And if the Republicans prevail in the
contested US presidential elections, they will likely reverse an earlier
decision allowing such research to be publicly funded.
While these moves may be motivated by the best intentions, they could delay
long-awaited advances by years. Researchers are trying new approaches to avoid
this ethical conundrum—they are making huge strides in finding new sources
of stem cells, for instance. But without the knowledge that might be gained from
studying embryonic stem cells, many of these efforts will be wasted.
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When the full potential of embryonic stem cells is realised, surgeons will
use them in the same way sculptors use clay. Taken from a very early embryo, and
given the right chemical or protein signals, they can be shaped into any tissue
or replace any damaged cells.
However, pro-life campaigners are telling governments to stop this line of
research. They argue that an embryo, even if it has only eight cells, is a human
life. Destroying it is murder.
Film director and former “Superman” Christopher Reeve, who became paralysed
from the neck down in 1995, disagrees. “This has nothing to do with abortion,”
he told a packed auditorium at this year’s Society for Neuroscience meeting in
New Orleans. Reeve urged researchers to “have the courage” to proceed to human
trials with various promising therapies for paralysis, including those using
stem cells to regrow nerve tissue.
Time may be short, however. In August, President Bill Clinton allowed
publicly funded research into embryonic stem cell research to go ahead in the US
with certain restrictions, a move hailed by scientists. But pressure from
Republicans in the US Congress has severely limited funding for such research.
And George W. Bush’s aides say he wants to reverse Clinton’s decision.
Republicans retain a slim majority in Congress, so any more loosening of
restrictions in the near future seems unlikely.
Such delays in opening up embryonic stem cell research could have a
profound effect. For the first time, there is a feeling of optimism among
neuroscientists that real progress can be made in developing therapies against a
host of neurological afflictions. Stem cells are helping researchers develop
exciting potential therapies for brain injury, stroke and diseases such as
multiple sclerosis and motor neuron disease.
Each year, 2 million people suffer head injuries in the US, says Tracy
McIntosh of the University of Pennsylvania. And there is no available treatment,
bar drilling a hole in the head, he says. “The Incas did that 10,000 years
.”
His group induced the equivalent of concussion in 48 mice. Three days later
they injected either mouse neural stem cells or human kidney cells—as a
control—into the animals’ brains. After five weeks, mice given the stem
cells showed a significant improvement in cognitive function, as measured by
their ability to navigate a water maze, he told the New Orleans conference.
Such work depends on embryonic stem cells. In Britain, a
proposed relaxation of the 1990 Human Fertilisation and Embryology Act would
give researchers even more freedom than in the US. They could take stem cells
from embryos up to two weeks old, just before the nervous system begins to form.
And it would allow “therapeutic cloning”—fusing an adult cell with an egg
stripped of its nucleus to make an embryo, from which stem cells could be
harvested.
But as in the US, such proposals face staunch opposition from pro-life MPs
who say making embryos for spare parts is morally repugnant. They also argue
that therapeutic cloning is one short step from reproductive cloning, which
would create an entirely new person.
Two weeks ago in Westminster, these concerns scuttled a private member’s bill
that would have allowed stem cells to be isolated from embryos. Although private
member’s bills rarely result in a change to the law, Conservative MP Edward
Leigh forced the bill to a vote after only ten minutes of debate. That was too
little time, supporters say, to make MPs aware of all the facts. Parliament will
hold a free vote later this year on whether to extend the 1990 act.
Yet embryonic stem cells have already led to advances in treating the animal
equivalent of motor neuron disease, which eventually leaves humans unable to
move. Jeffrey Rothstein at Johns Hopkins University in Baltimore, Maryland,
found that paralysed rats given an injection of embryonic stem cells into the
spinal fluid dramatically regain partial leg movement. Evan Snyder of Harvard
Medical School in Boston has also made progress in using stem cells to kill off
cancerous brain cells.
Clinical trials for treating Huntington’s disease are also starting to bear
fruit. Marc Peschanski from the Créteil laboratory of INSERM, the French
National Health and Medical Research Institute, has given five patients
eight-day-old fetal stem cells that had already begun differentiating into
nervous tissue. Implants of the cells into the striatum, a brain region that
helps control movement, improved movement and cognitive function in three of the
five patients, he told the conference. “Long-term clinical improvements are
possible,” he says.
These advances are founded on embryonic stem cell research. Many who object
to the use of this tissue say the whole ethical morass could be avoided by
sticking to non-embryonic stem cells. These reside in every tissue in the body
and replace old cells when they die. So far about 20 kinds have been discovered,
and they can be harvested from cadavers, blood and even skin.
Snyder has used stem cells harvested from newborn mice to treat stroke, where
a localised region of the brain is damaged. His treatment exploits the special
ability of stem cells to home in on sites of injury. Snyder’s team induced a
stroke in adult male rats by briefly cutting off the main cerebral artery. One
day later, they injected them in the back of the brain with either stem cells, a
growth factor, or both. These migrated to the injury site, and all the rats
showed some recovery, according to three standard tests of motor function. The
rats on the combined therapy did best.
Jeffery Kocsi of Yale University in New Haven, Connecticut, is using adult
stem cells to treat multiple sclerosis. In MS, the insulating sheath of myelin
that surrounds nerve fibres dies, disrupting nerve transmission.
He used X-rays and injections of a toxic chemical to damage discrete areas of
myelin in adult marmosets. He then took stem cells from the subventricular zone
of the monkeys’ brain, added some growth factors, and injected them back into
the affected region. Three weeks later there was “extensive remyelination”.
Kocsi has high hopes for auto-transplantation therapy to treat demyelinating
diseases. “Even a 5 or 10 per cent improvement would significantly affect human
quality of life,” he says.
Turning paralysis from a permanent to a treatable condition is one of
neuroscience’s greatest prizes. Researchers are making advances on a number of
fronts, and one of the most promising involves stem cells.
Fred Gage of the Salk Institute in La Jolla, California, says cell
transplants can help regenerate nerves. The adult central nervous system
produces its own stem cells, but they only become neurons in a couple of places
in the body. We need to understand how to make them work for us, says Gage, so
we can regenerate neurons wherever they are damaged.
If stem cells are taken from the spinal cord and placed in the part of the
brain where neurons are born, they become capable of differentiating into
neurons. And scientists are close to working out which molecules in surrounding
tissues are responsible. Gage says teasing out this mechanism will be critical
if we are to develop treatments for paralysis.
But even though rapid progress is being made in developing sources of adult
stem cells and treatments that use them, these cells are not as versatile as
embryonic cells. Skin stem cells can only make skin. Neural stem cells can only
make neurons. Most are difficult to harvest and don’t live long in cell culture
dishes. So far, most of the successful experiments in rats with stem cells have
used the embryonic variety.
In August, Ira Black at the Robert Wood Johnson Medical School in New Jersey
reported that he had converted bone marrow stem cells into the precursors of
neurons. This makes adult stem cells more attractive, since marrow is easier to
harvest.
But Black says we will never know what biochemical cues give cells their
identity unless researchers can study embryonic stem cells—the most
undifferentiated cells of all. Limiting research to adult stem cells would leave
scientists groping in the dark. “We don’t yet know enough even to ask the proper
questions,” he says.
Neuroscientists still face formidable challenges. Many cells die, for
example, and some go to the wrong place or become the wrong kind of cell.
Rothstein says we still don’t know how long implanted stem cells survive, or
whether some will become tumours due to their extraordinary ability to keep
dividing. It isn’t even clear when to implant such cells. These questions can
only be answered by testing stem cells over and over in the lab—and
embryonic cells are the only type suitable, say researchers.
Ironing out these kinks is a key issue in developing therapies for
neurological diseases. Last week, Britain’s Royal Society reaffirmed the need
for more work on embryonic cells, calling for scientists to be allowed to grow
stem cells from embryos younger than 14 days.
Such research could be critical. Neuroscientists are a cautious bunch and
fear that offering even a hint that they could cure brain disease, spinal injury
and stroke simply raises patients’ hopes prematurely. But this year the
20,000-plus neuroscientists who gathered in New Orleans let slip their optimism
that repairing damage to the brain and spine is finally within reach.
Christopher Reeve summed up the mood. “There is no reason why this problem
and other disorders of the brain and central nervous system can’t be overcome,”
he told the meeting. Researchers agree. “We can do it soon. We must do it soon,”
said Dennis Choi, outgoing president of the society.
It remains to be seen just how much progress politicians will allow
scientists to make. “Scientists know a lot, but the obstacle of politics will
affect implementation,” says Reeve. “What happens in a Bush presidency, God
ڴǰ.”
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