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A few years ago, Dr. Ellen Heber-Katz, an immunologist at
the Wistar Institute in Philadelphia, was conducting an
experiment with those mice, which develop a disease similar to
lupus. As is common, Dr. Heber-Katz punched a pattern of holes
in each mouse's ear to so she could tell which mouse was
Three weeks later, she said, when she checked on the
experiment, "there were no ear holes." Dr. Heber-Katz could
not tell the mice apart. That ruined her experiment but sent
her into a whole new field of study.
She has since found that those mice, unlike other mice, can
also regrow parts of their hearts, tails and spinal cords. The
fact that the "healer mice" do not form scars appears to be
important, she said. Scars block the ability of cells to
divide and block signals from the epidermis, a layer of skin,
that appear necessary to begin regeneration, she said.
Scientists have been fascinated by regeneration since the
1700's, when a French scientist, René-Antoine Ferchault de
Réaumur, for whom a temperature scale is named, noticed at the
fish market that some crayfish had legs that were not the same
size. He surmised that some legs had grown back after having
been cut off. Other scientists around the same time found that
hydra, snails and other creatures could regenerate, setting
off a frenzy of experimentation.
"Almost everything that moved in Europe was amputated,"
said Dr. Alejandro Sánchez Alvarado, an associate professor of
neurobiology and anatomy at the University of Utah. Even
Voltaire decapitated a snail to see its head grow back. He
then wrote to friend who was blind that he hoped that a
similar process could be harnessed in people.
But that has proved difficult. Dr. Thomas Hunt Morgan
studied regeneration at the beginning of the 20th century and
basically declared the subject intractable. Dr. Morgan himself
moved on to other areas, studying genes and chromosomes in the
fruit fly, work that won him a Nobel Prize as the father of
Now, scientists hope to understand regeneration by finding
the genes involved. Dr. Heber-Katz has found at least seven
locations on the chromosomes of her "healer mice" that appear
to contain genes that correlate with the ability to
Dr. Sánchez Alvarado is systematically turning off genes in
planaria in hope of discovering which are necessary for
regeneration. Dr. David Stocum, a biology professor and the
dean of the School of Science at Indiana University-Purdue
University Indianapolis, is studying which genes are active in
tadpoles, which can regrow limbs, but not in adult frogs,
One gene that appears to be important is msx1. It helps
keep cells in an embryo from dividing prematurely. Dr. Keating
found that when the gene was turned on in mouse muscle cells
that were growing in culture, the cells de-differentiated into
stem cells. Another tantalizing clue of the importance of
msx1, Dr. Keating said, is that the gene is turned off in
people, except in the fingertips, the one part of the body
where regeneration has been seen.
Dr. Keating has also made mouse muscle cells
de-differentiate by using an uncharacterized mixture of
proteins extracted from a newt. Scientists at the Scripps
Research Institute did that with a chemical called myoseverin.
The scientists focusing on natural regeneration concede
that stem cell scientists are highly likely to make more
progress in the near future.
"It's a lot easier to take a stem cell and put it back
somewhere than to figure out what's going on here," Dr.
But the salamander types insist that their time will
"Given that these mechanisms work so well in animals that
are built like us," Dr. Brockes said, "it would really
surprise me if there wasn't some role for this strategy in the