RVINE, Calif. — In a closetlike room at the "Leg Lab"
here, salamanders stare blankly out of clear plastic drinking
cups. The lab is so named because many of the animals have
had, or will have, a leg cut off. But the salamanders recover,
with perfect new limbs growing back in weeks.
Salamanders are the superstars of regeneration. They can
grow back not only limbs but also tails, parts of their hearts
and the retinas and lenses in their eyes. Humans cannot do any
of that. So scientists here hope that the salamander's tricks
may one day be applied to people.
"I really do believe it's just a matter of time before
you're going to regenerate an arm or at least a finger," said
Dr. David M. Gardiner, a biologist who runs the laboratory at
the University of California at Irvine with Dr. Susan V.
Bryant, the dean of biological sciences and his wife. "I'd
like to see that in my lifetime."
Regenerative medicine, regrowing or repairing damaged
organs, has become a hot topic. Almost all the attention has
focused on stem cells. The idea is to grow stem cells outside
the body, turn them into particular types of tissue and
transplant them into patients.
But a few scientists theorize that a better approach is to
induce the same regeneration in people that occurs in
salamanders and some other animals. Natural regeneration,
which might be accomplished with drugs or genes, would be
easier than transplanting, they say. And the tissue would be
the patient's own, doing away with the problem of rejection.
Even if salamanders' feats cannot be reproduced in humans,
those scientists say, studying regenerating animals will at
least provide clues for stem cell scientists.
So far, natural regeneration remains a medical backwater,
garnering little attention. That may be understandable.
Scientists have been studying natural regeneration for 200
years and have not gotten far in understanding it. Regrowing
human arms in the lifetime of Dr. Gardiner, who is 53, will be
"I'd like to say we've made tremendous progress, but that
would be a lie," said Dr. Catherine Tsilfidis, an assistant
professor at the University of Ottawa Eye Institute, who is
studying regeneration in newts.
Now, though, genetic techniques are starting to allow
scientists to fathom the mechanisms of regeneration. That and
the excitement surrounding regenerative medicine are creating
new scientific and even commercial interest in
Eli Lilly is supporting research aimed at finding genes
that help amphibians regenerate, and venture capitalists
recently invested $9 million in starting what is perhaps the
first company that wants to replicate natural regeneration in
The company, Hydra Biosciences, is largely based on the
work of Dr. Mark T. Keating, a company founder and a biologist
at Harvard who studies regeneration in zebrafish. Hydra of
Cambridge, Mass., is named after a pond-dwelling creature that
can grow two wholes after being sliced in two. That creature
was in turn named for the mythical multiheaded serpent that
regrew new heads when one was cut off.
"What we're trying to do is stimulate the body's natural
ability to regenerate," Dr. Keating said. "There's no evidence
that human cells are fundamentally different" from those of
Humans can regenerate some parts like livers, muscles and
bones, but human regeneration is generally limited to single
types of tissues. Salamanders can regrow multiple types of
tissue to make complete structures like limbs. The planarian,
a small flatworm, can be cut into pieces as small as one-279th
of the whole, and entire new worms will grow from the
The one possible example of multitissue regeneration in
people is that young children can regrow fingertips above the
top joint, including the bone, skin and nail. That was
discovered by accident in England in 1974, when a child who
lost a fingertip in a farm accident was taken to a hospital.
The doctor was too busy to provide the standard treatment,
sewing the skin closed. When she got around to it over a day
later, she saw that it was regrowing.
Still, some experts say, that may not be true regeneration
but rather a continuation of the fast growth that normally
occurs in children's fingers.
Scientists say animals that regenerate do not do it the way
scientists are now hoping to do it in people — by finding stem
cells in the body that can be extracted or induced to turn
into specific types of tissue. "The reason they can do this,
we think, is not because they are chock-full of stem cells
waiting to blast forth after an injury," said Prof. Jeremy
Brockes of University College London.
Rather, he said, it appears that cells near the site of the
injury that are already specialized like muscle cells lose
their specialized properties and revert to a primordial state
in a process called de-differentiation. The animal, in effect,
creates its own stem cells when they are needed.
Those stem cells form a mound called a blastema and
multiply rapidly. They then redifferentiate to form the tissue
needed to rebuild the limb or organ.
Scientists wonder why the ability to regenerate has not
spread more widely through evolution. "It seems the higher up
you move in terms of evolution," Dr. Tsilfidis said, "the less
One reason, she speculated, is that higher animals depend
more on specialized cells to perform sophisticated functions,
and those cells are harder to de-differentiate. Or, she said,
the advanced immune systems of higher life forms may mistake
rapidly proliferating cells for cancer and kill them.
There are hints that this type of regeneration can occur in
higher animals. Dr. Thomas A. Reh, a professor of biological
structure at the University of Washington, found that neurons
in a chicken retina could be replenished because other nerve
cells called glial cells de-differentiated. In the distant
future, Dr. Reh said, that may be used to help heal blindness
caused by retinal diseases like macular degeneration.
Regeneration has been found in mammals, in a strain of mice
with an altered immune system.