Otto Loewi
This is a passage from Loewi's larger work An Autobiographic Sketch published in the journal Perspectives in Biology and Medicine, Vol. 4, No. 1, Autumn 1960.
Now I have to turn to the best known of my scientific achievements, the establishment in 1921 of the chemical theory of the transmission of the nervous impulse. Until 1921 it was generally assumed hat transmission was due to the direct spreading of the electrical wave accompanying the propagated nervous impulse from the nerve terminal to the effector organ. Since the character of that potential is everywhere the same, such an assumption would not explain the well-known fact that the stimulation of certain nerves increases the function of one organ and decreases the function of another. A different mode of transmission had, therefore, to be considered.
As far back as 1903, I discussed with Walter M. Fletcher from Cambridge, England, then an associate in Marburg, the fact that certain drugs mimic the augmentary as well as the inhibitory effects of the stimulation of sympathetic and/or parasympathetic nerves on their effector organs. During this discussion, the idea occurred to me that the terminals of those nerves might contain chemicals, that stimulation might liberate them from the nerve terminals, and that these chemicals might in turn transmit the nervous impulse to their respective effector organs. At that time I did not see a way to prove the correctness of this hunch, and it entirely slipped my conscious memory until it emerged again in 1920.
The night before Easter Sunday of that year I awoke, turned on the light, and jotted down a few notes on a tiny slip ofthin paper. Then I fell asleep again. It occurred to me at six o'clock in the morning that during the night I had written down something most important, but I was unable to decipher the scrawl. The next night, at three o'clock, the idea returned. It was the design of an experiment to determine whether or not the hypothesis of chemical transmission that I had uttered seventeen years ago was correct. I got up immediately, went to the laboratory, and performed a simple experiment on a frog heart according to the nocturnal design. I have to describe briefly this experiment since its results became the foundation of the theory of chemical transmission of the nervous impulse.
The hearts of two frogs were isolated, the first with its nerves, the second without. Both hearts were attached to Straub cánulas filled with a little Ringer solution. The vagus nerve of the first heart was stimulated for a few minutes. Then the Ringer solution that had been in the first heart during the stimulation of the vagus was transferred to the second heart. It slowed and its beats diminished just as ifits vagus had been stimulated. Similarly, when the accelerator nerve was stimulated and the Ringer from this period transferred, the second heart speeded up and its beats increased. These results unequivocally proved that the nerves do not influence the heart directly but liberate from their terminals specific chemical substances which, in their turn, cause the well-known modifications of the function of the heart characteristic of the stimulation of its nerves.
The story of this discovery shows that an idea may sleep for decades in the unconscious mind and then suddenly return. Further, it indicates that we should sometimes trust a sudden intuition without too much skepticism. If carefully considered in the daytime, I would undoubtedly have rejected the kind of experiment I performed. It would have seemed likely that any transmitting agent released by a nervous impulse would be in an amount just sufficient to influence the effector organ. It would seem improbable that an excess that could be detected would escape into the fluid which filled the heart. It was good fortune that at the moment of the hunch I did not think but acted immediately.
For many years this nocturnal emergence ofthe design ofthe crucial experiment to check the validity of a hypothesis uttered seventeen years before was a complete mystery. My interest in that problem was revived about five years ago by a discussion with the late Ernest Kris, a leading sychoanalyst. A short time later I had to write my bibliography, and glanced over all the papers published from my laboratory. I came across two studies made about two years before the arrival of the nocturnal design in which, also in search of a substance given off from the heart, I had applied the technique used in 1920. This experience, in my opinion, was an essential preparation for the idea of the finished design. In fact, the nocturnal concept represented a sudden association of the hypothesis of 1903 with the method tested not long before in other experiments. Most so-called "intuitive" discoveries are such associations suddenly made in the unconscious mind.