The Raelian Movement
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Two New Paths to the Dream: Regeneration
http://www.nytimes.com/2010/08/06/science/06cell.html
By NICHOLAS WADE
Published: August 5, 2010
Two research reports published Friday offer novel approaches to the
age-old dream of regenerating the body from its own cells.
Animals like newts and zebra fish can regenerate limbs, fins, even
part of the heart. If only people could do the same, amputees might
grow new limbs and stricken hearts be coaxed to repair themselves.
But humans have very little regenerative capacity, probably because of
an evolutionary trade-off: suppressing cell growth reduced the risk of
cancer, enabling humans to live longer. A person can renew his liver
to some extent, and regrow a fingertip while very young, but not much
more.
In the first of the two new approaches, a research group at Stanford
University led by Helen M. Blau, Jason H. Pomerantz and Kostandin V.
Pajcini has taken a possible first step toward unlocking the human
ability to regenerate. By inactivating two genes that work to suppress
tumors, they got mouse muscle cells to revert to a younger state,
start dividing and help repair tissue.
What is true of mice is often true of humans, and although scientists
are a long way from being able to cause limbs to regenerate, the
research is attracting attention. Jeremy Brockes, a leading expert on
regeneration at University College London, said the report was "an
excellent paper." Though there is a lot still to learn about the
process, "it is hard to imagine that it will not be informative for
regenerative medicine in the future," he said.
In recent years, most research in the field of regenerative medicine
has focused on the hope that stem cells, immature cells that give rise
to any specific type of cell needed in the body, can somehow be
trained to behave as normal adult cells do. Nature's method of
regeneration is quite different in that it starts with the adult cells
at the site of a wound and converts the cells to a stemlike state in
which they can grow and divide.
The Stanford team has taken a step toward mimicking the natural
process. "What I like is that it's built on what's happening in
nature," Dr. Blau said. "We mammals lost this regenerative capacity in
order to have better tumor suppression, but if we reawaken it in a
careful way we could make use of it in a clinical setting."
Dr. Pomerantz, a clinician, hopes the technique can be applied to
people, though many more animal experiments need to be done first. "We
have shown we can recapitulate in mammalian cells behavior of lower
vertebrate cells that is required for regeneration," he said. "We
would propose using it in amputations of a limb or part of a limb or
in cardiac muscle." After a heart attack, the muscle cells do not
regenerate, so any method of making them do so would be a possible
treatment.
Interfering with tumor suppressor genes is a dangerous game, but Dr.
Pomerantz said the genes could be inhibited for just a short period by
applying the right dose of drug. When the drug has dissipated, the
antitumor function of the gene would be restored.
Finding the right combination of genes to suppress was a critical step
in the new research. One of the two tumor suppressor genes is an
ancient gene, known as Rb, which is naturally inactivated in newts and
fish when they start regenerating tissue. Mammals possess both the Rb
gene and a backup, called the Arf gene, which will close down a
cancer-prone cell if Rb fails to do so.
The Stanford team found that newts did not have the Arf backup gene,
which mammals must have acquired after their lineage diverged from
that of amphibians. This suggests that the backup system "evolved at
the expense of regeneration," the Stanford researchers say in Friday's
issue of Cell Stem Cell.
The Stanford team shut off both Rb and Arf with a chemical called
silencing-RNA and found the mouse muscle cells started dividing. When
injected into a mouse's leg, the cells fused into the existing muscle
fibers, just as they are meant to.
The Stanford researchers have learned how to block two genes thought
to inhibit the natural regenerative capacity of cells, but it is
somewhat surprising that the regenerative mechanism should still exist
at all if mammals have been unable to use it for 200 million years.
"One school of thought is that regeneration is a default mechanism and
doesn't require its own program," Dr. Pomerantz said.
Dr. Brockes believes that this is true in part. Regeneration "depends
on a largely conserved cellular machinery," he said, meaning that it
is present in all animals. The machinery comes into play in wound
healing and tissue maintenance. But specific instances of
regeneration, like regrowing a whole limb, are invoked by genes
specific to various species. He has found a protein specific to
salamanders that coordinates regrowth of a salamander limb.
If the regeneration of a whole limb is a special ability that
salamanders have evolved, then humans would not have any inherent
ability to do the same. "I would beware of suggesting that this sort
of manipulation is capable of unlocking 'the newt within,' " Dr.
Brockes said.
A second, quite different approach to regenerating a tissue is
reported in Friday's issue of Cell by Deepak Srivastava and colleagues
at the University of California, San Francisco. Working also in the
mouse, they have developed a way of reprogramming the ordinary tissue
cells of the heart into heart muscle cells, the type that is
irretrievably lost in a heart attack.
The Japanese scientist Shinya Yamanaka showed three years ago that
skin cells could be converted to embryonic stem cells simply by adding
four proteins known to regulate genes. Inspired by Dr. Yamanaka's
method, Dr. Srivastava and his colleagues selected 14 such proteins
and eventually found that with only three of them they could convert
heart fibroblast cells into heart muscle cells.
To make clinical use of the discovery, Dr. Srivastava said he would
need first to duplicate the process with human cells, and then develop
three drugs that could substitute for the three proteins used in the
conversion process. The drugs could be loaded into a stent, a small
tube used in coronary bypass operations. With the stent inserted into
a heart artery, the drugs would convert some of the heart's tissue
cells into heart muscle cells.
Some researchers hope that with Dr. Yamanaka's method of turning skin
cells into embryonic stem cells, those stem cells can be converted
into usable heart muscle cells. One problem with this approach is that
any unconverted embryonic stem cells may form tumors. Dr. Srivastava's
method sidesteps this problem by avoiding the stem cell stage.
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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.
There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.
On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.
Rael
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