observation is compatible with Bernstein's hypothesis (the polarities of all damaged cells should be the
same and they should persist no longer than the time required to repair or replace the damaged cells),
but they are compatible with the concept of an organized neural DC control system with actual current
flow.
On the basis of these observations we theoretically divided regeneration into two separate but
sequential phases; the first being the formation of a blastema in response to a signal that is stimulating
to the local cells and through their dedifferentiation produces the blastema. The information content of
the signal responsible for the first phase is obviously sparse and the signal may be correspondingly
simple, whereas the signal responsible for the second phase must be capable of carrying an enormous
amount of information (what structure is to be formed, what its orientation with respect to the rest of
the body is to be, and finally all of the details of its complex structure).
In our view, the DC potentials and currents generated at the site of injury by the DC control
system were quite suitable as the signal for the first phase, whereas their information content was
totally inadequate for the second phase. This concept meant that there could be two mechanisms at
fault in those animals normally incapable of regenerative growth. First the initial phase may fail to
produce a blastema because of either an inadequate signal or an inability of the cells to respond to an
adequate signal by dedifferentiation. If an adequate blastema was formed, the second phase
informational signal might be missing or inadequate to produce the subsequent redifferentiation and
growth. Since it is common knowledge that nonregenerating animals fail in the first phase and do not
produce blastemas, and in view of our finding of the polarity differences between regenerators and
nonregenerators in the first phase, we postulated that the initial stimulating signal was missing in the
nonregenerating animals. Simulation of this signal by external means was technically quite feasible;
however, one could not predict whether the cells would be capable of responding to it or if they did,
and a blastema was formed, whether the complex informational signal that controlled the second phase
would be present.
The first test of this hypothesis was provided by Smith, who implanted simple bimetallic
electrical generating devices (a short length of platinum wire soldered to a short length of silver wire)
in amputated forelegs of adult frogs (40). In 1967 he reported the successful stimulation of partial limb
regeneration by this technique. Theorizing that the failure to regenerate completely was due to the
device being fixed in position at the original amputation level, he repeated the experiment using a
device that had extensible electrode leads and in 1974 he reported securing regeneration of a complete
extremity in the same animal (41). Meanwhile, we applied a modification of Smith's device to the
foreleg amputation in the rat, reporting in 1972. the regeneration of the forelimb from the amputation
level midway between the shoulder and elbow, down to and including the elbow joint complete in all
anatomical detail (42). This was the first successful stimulation of the regeneration of a complex
extremity by artificial means in a mammal. It has subsequently been substantiated by Libben and
Person in 1979 (43) and by Smith in 1981 (44), all using similar techniques.
ELECTROMAGNETISM & LIFE - 34