DAVID NACHMANSOHN 



be subdivided into three successive phases: a stimulus reaching a 

 neuron must initiate an impulse; the impulse, once initiated, must 

 be propagated along the axon; and, finally, it must be transmitted 

 either to a second neuron or to an effector cell. Early in this century, 

 the idea was evolved that a chemical compound may be connected with 

 the third phase, namely, the transmission of the nervous impulse from 

 the nerve ending to the effector cell. T. R. Elliot suggested, in 1905, 

 that adrenalin may be the transmitter of the impulse from the sympa- 

 thetic nerve ending to the effector cell. He based this idea on the 

 similarity between the action of adrenalin and the effect of stimulation 

 of sympathetic nerves. In 1921, Otto Loewi discovered that, follow- 

 ing vagus stimulation of the frog's heart, a compound appeared in the 

 perfusion fluid which, if transmitted to a second heart, produced an 

 effect similar to that of vagus stimulation. Accepting the basic idea 

 of Elliot, Loewi concluded that the compound (which was later identi- 

 fied with acetylcholine) is actually liberated from the nerve ending 

 and acts as a transmitter of the vagus impulse to the heart cell. Loewi's 

 concept of "neurohumoral" transmission was widely accepted among 

 physiologists. 



In 1933, Dale tried to extend this idea of a "chemical media- 

 tor" of the nerve impulse to the neuromuscular junction and to the 

 ganglionic synapse. His theory was based essentially on the same 

 type of evidence as previously applied by Loewi in the case of auto- 

 nomic nerves. In this instance, however, the theory encountered 

 strong opposition. Besides many contradictions and difficulties there 

 were two main objections. The first was the time factor. This factor 

 was of lesser importance in the case of the slowly reacting cells in- 

 nervated by the autonomic nervous system. But the transmission of 

 nerve impulses across neuromuscular junctions and ganglionic synapses 

 occurs within milliseconds. No evidence was available that the 

 chemical process can occur at the high speed required, and Dale and 

 his associates admitted this difficulty. The second objection was still 

 more fundamental. According to leading neurophysiologists like 

 Sherrington, Fulton, Gasser, and Erlanger, the excitable properties of 

 axon and cell body are basically the same. The electric signs of 

 nervous action therefore did not support the assumption that the 

 transmission of the nerve impulse along the axon differs fundamentally 

 from that across the synapse (6). 



