X-Message-Number: 984
Newsgroups: sci.cryonics
From:  (kevin.q.brown)
Subject: The Difference Between Us and Salamanders
Date: Mon, 14 Jul 1992 17:41:52 GMT
Keywords: self-repair NCAMs

[ One thing that is certain about cryonic suspension is that a lot
  of repair will be needed to reanimate anyone frozen with today's
  suspension methods.  Some organisms, such as salamanders, have
  self-repair capabilities that may be useful to humans, if only we
  can figure out how to transfer those capabilities to humans.
  This message from a recent issue of Periastron describes progress
  in our understanding of how salamander's self-repair capability
  works. It is posted with permission of the author Thomas Donaldson
  <>. - KQB ]

THE DIFFERENCE BETWEEN US AND SALAMANDERS
by Thomas Donaldson
Periastron, P.O. Box 2365, Sunnyvale, CA 94087  USA

For many years now scientists have known that salamanders have far more
ability to repair themselves than any human being.  The most visible sign
of this comes from their ability to regrow a tail or limb if one has been
torn off.  They have a similar ability, less visible, to repair their own
brain if it has been cut and even scrambled a bit.

For any application to medicine, some way to create those same abilities
artificially in human beings would have tremendous benefits.  Yet up to
quite recently no one has even had a hint about just why such an extreme
different exists.  Means to help repair spinal cords and injured brains
still seem far away, means to regrow a lost leg just as far.

Recently however an interesting paper in NATURE (P Doherty, SV Ashton,
CECK Moolenaar, and others, NATURE (356)(1992) 791-793) presents evidence
about one chemical factor which may account for some of our repair
inability.

By now scientists have isolated several chemical factors which promote
and guide growth in embryonic brains (and other tissue, too).  One
prominent class of such factors are the NCAMs (already discussed in this
issue: see the first article).  NCAM stands for Neural Cell Adhesion
Molecule.  NCAMs are a family of protein molecules which cause outer
neuron surfaces to stick together.  In embryos, they not only cause this
sticking effect but actually promote and guide neuron growth,
particularly the growth of processes out of the neural cell body (both
dendrites and axons).  NCAMs have one other distinguishing trait: rather
like the immunoglobins in our immune system, their proteins sequence
allows for variability.  For NCAMs this means that each NCAM gene can
produce 20 to 30 different proteins, depending on just how the NCAM
protein is spliced together from its parts.

The authors of this paper single out one gene part which (combined with
the rest of the NCAM gene) can create a special form of NCAM 140.  They
call this the "Variable Alternatively Spliced Exon", or VASE (our genes
consist of two kinds of sequences: introns, which may play a guiding role
but don't actually act as a template for any part of the protein(s) the
gene produces, and exons, which DO act as templates for a protein or part
of one).

Doherty, Ashton, Moolenaar, and their colleagues show, in their paper,
two things.  First, only about 3% of the NCAMs in embryonic brain tissue
contained the VASE sequence, while 50% if NCAMs in adult brain contained
it.  By performing direct experiments on embryonic brain cells, they
could show that NCAM-VASE would inhibit growth in embryonic cells too.
That is, the change in NCAM type acts directly to inhibit growth.

These experiments don't tell us just WHY our NCAMs change to the VASE
type.  They do tell us where to keep looking for the causes of our
inhibited neural growth as adults.  Furthermore, the authors of this
paper point out that several other chemical factors must play an
important role.  Polysialic acid also occurs in growing embryonic brain,
and seems to modulate the effect of NCAMs, VASE or not.  Other factors in
embryonic brain also promote neuron growth, among which are N-cadherin
and integrin.  As with many phenomena in our nervous system, calcium ions
play a role in growth, too.

While these NCAM-VASEs show much less ability to promote growth, they
still play an important role in adult nervous systems.  Their adhesive
ability remains unchanged.  They act in this way to hold together the
final form of our brain.  In embryonic brain, their influence on growth
seems to act indirectly, through biochemical effects on other processes
rather than through simple adhesion.  Their role in growth, development,
and its inhibition needs much more exploration.  This paper points to a
direction for that exploration.

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