54
The Body Electric
present is the digital computer, which deals with bits of data, signals
that, in essence, say either yes or no, 1 or 0. The number of such bits
needed to fully characterize the salamander forelimb is incalculable, ex-
ceeding the capacity of all known computers operating in unison.
The question of how this information is transferred is one of the hard-
est problems ever tackled by scientists, and when we fully know the
answer, we'll understand not only regeneration but the entire process of
growth from egg to adult. For now, we had best, as biologists them-
selves have done, skip this problem and return to it after addressing
some slightly easier ones.
It seems reasonable that understanding what comes out of the blastema
would be easier if we understood what goes into it, so the other major
questions about regeneration have always been: What stimulates the
blastema to form? And where do its cells come from?
The idea that dedifferentiation was impossible led to the related belief
that all regeneration had to be the work of neoblasts, or "reserve cells"
left over from the embryo and warehoused throughout the body in a
primitive, unspecialized state. Some biological bell supposedly called
them to migrate to the stump and form the blastema. There's evidence
for such cells in hydras and flatworms, although it's now doubtful that
they fully account for regeneration in these animals. However, no one
ever found any in a salamander. In fact, as long ago as the 1930s, there
was nearly conclusive evidence that they did not exist. Nevertheless,
anti-dedifferentiation dogma and the reserve cell theory were defended
fanatically, by Weiss in particular, so that many unconvincing experi-
ments were interpreted to "prove" that reserve cells formed the blas-
tema. When I started out, it was very dangerous for one's career even to
suggest that mature cells might create the blastema by dedifferentiating.
Because it was so hard to imagine how a blastema could arise without
dedifferentiation, the idea later developed that perhaps cells could
partially dedifferentiate. In other words, perhaps muscle cells could be-
come cells that looked primitive and completely unspecialized, but that
would then take up their previous lives as mature muscle cells after a
brief period of amnesia in the blastema. To fit the square peg into the
round hole, many researchers did a lot of useless work, laboriously
counting cell divisions to try to show that the muscle cells in the stump
made enough new muscle cells to supply the regenerate. The embarrass-
ing
blastema—enigmatic
and
completely
undifferentiated
was
still
there.
We now know (see Chapter 6) that at least some types of cells can
revert completely to the primitive state and that such despecialization is