effect the electron transfer. Compounds of the same steric property but lacking the electron transfer
capability were not carcinogenic. Except for this work of Huggins and Yang all other reports of growth
effects of actual electrical currents could not be placed in a frame of reference that was acceptable to
the scientific establishment.
The demonstration of the existence of intrinsic electrical currents and particularly their
localization to the nervous system permitted the problem to be viewed in a new light. It had been a
long-standing clinical observation that healing was delayed and often defective in areas that were
deficient in innervation. With the idea that the nervous system in some ways possessed a growth-
controlling function, Hasson reasoned that there should be a similar relationship between denervation
and tumor formation (32). In 1958 he reported that tumor induction by carcinogenic agents was
facilitated by denervation, and these observations were subsequently confirmed in 1967 by Pawlowski
and Weddell (33).
By the mid-1950's Singer published a series of papers in which he demonstrated the dependence
of limb regeneration in the salamander on the presence of a threshold amount of nerve tissue in the
amputation stump (34). He was even able to produce a small amount of limb regeneration in the adult
frog (normally a nonregenerator) by transplanting additional functioning nerve tissue into an
amputation stump. The evidence suggested that the nerves somehow controlled normal growth; in their
absence normal growth was inhibited and abnormal growth was facilitated. None of these observations
made much sense under the nerve impulse concept of neural functioning-in fact nerves to a healing area
are usually "silent," with very little action potential traffic. However, when the previous reports of the
growth controlling properties of direct currents were combined with the localization of the intrinsic DC
system to the nerves, the relationships between the nervous system and growth began to make some
sense.
This relationship is particularly clear in the area of regenerative growth, where considerable
research has now been conducted over the past two decades. Regeneration is the most dramatic and
important of the growth/ healing processes, being the actual regrowth of missing parts in full
anatomical detail. It is most common in the lower animals-the salamander limb regeneration
preparation being the one most frequently used in research- and it diminishes as one ascends the
evolutionary scale. In the human, true regeneration is limited to the healing of fractures of the long
bones; other processes commonly called regenerative (i.e., skin and peripheral nerve fiber) are simply
increased rates of cellular multiplication or growth. The essence of the true regenerative process is the
appearance at the site of injury of a mass of primitive, presumably totipotent cells, called the blastema.
After reaching a critical size this cellular mass begins to grow in length and to redifferentiate to
produce the multicellular, multitissue, complex missing structure. The capability of the process is best
indicated by noting that the salamander foreleg is anatomically equivalent to the complex human arm.
Regeneration was first formally reported by Spallanzini in 1768 and has been the subject of
study ever since, with many attempts being made to restore the process to animals normally lacking it.
The first successful attempt was reported by Rose in 1944 when he produced a small measure of
regeneration of the amputated foreleg of the frog (a species that, despite folk-lore, cannot regenerate an
extremity) by dipping the extremity daily in hypertonic saline (35). Two years later, a similar result was
reported by Polezhayev (36) in the same animal, by repeatedly needling the stump daily. While it was
the intent of both of these investigators to delay the overgrowth of skin over the end of the amputation
stump, the procedure used in each experiment was obviously repeatedly traumatic. Ten years later
Singer, again using the amputated foreleg of the adult frog, obtained the same amount of regeneration
by surgically augmenting the nerve supply to the extremity. There seemed to be little relationship
ELECTROMAGNETISM & LIFE - 32