Reflections on the Pioneers of Neurohumoral Transmission

REFLECTIONS ON THE PIONEERS OF NEUROHUMORAL TRANSMISSION GEORGE B. KOELLE* In 1950 I graduated from The Johns Hopkins Medical School and received a travel award to the XVIIIth International Physiological Congress in Copenhagen. I decided to turn this windfall into a condensed 2month wanderjahr. At the federation meeting that spring in Atlantic City, I had met Otto Loewi (about whom more later) and asked him what was the most beautiful place in Europe. He replied unequivocally the Engadine Valley in Switzerland; I included this in my itinerary and was not disappointed. When I reached London, my host was my former Hopkins associate, J. Peter Quilliam. After taking me on the rounds of the pharmacology departments there, as well as the former site of 22 IB Baker Street (now occupied by an office building), he drove me to the meeting of the British Physiological Society at Oxford. We were informed that we had been billeted in New College. I was delighted with the thought of a modern glass and steel structure but soon learned that this college had been erected in approximately 1 150, in contrast with the Old College, which dated somewhat earlier. The porter escorted us to our room on the top floor. As he was leaving, I asked where we might take a bath. He turned around, glared, and stated: "You're only going to be here for three days. You don't want a bath!" Abashed, I mumbled, "Oh, no; certainly not; wouldn't think of such a thing." He nodded and left. The next three days were truly exciting. I met a host of neurohumoral scientists whose names I had known from the literature: Hugh Blaschko, Edith Bulbring, G. L. Brown, Harold Burn, Gladwyn Buttle, Sir Henry Dale, William Feldberg, John Gaddum, H. R. Ing, and Marthe Vogt. I This paper is based on a talk given at the banquet of the VIIth International Congress of Histochemistry and Cytochemistry hosted by Professor Olavi Eränkö, August 9, 1984, Helsinki, Finland. ""Department of Pharmacology, Medical School/G3, University of Pennsylvania, Philadelphia , Pennsylvania 19104.© 1985 by The University of Chicago. AU rights reserved. 003 1-5982/85/2803-0436$0 1.00 434 J George B. Koelle · Pioneers of Neurohumoral Transmission also met a number of contemporaries who subsequently became famous for their work in this field, including Arnold Burgen, Olavi Eränkö, Avram Goldstein, Bo Holmstedt, Nicky Karczmar, Hank Macintosh, Walter Perry, Bill Paton, John Vane, Peter Waser, and Nora Zaimis. Most of the foregoing assembled again in Philadelphia 3 years later for a Symposium on Neurohumoral Transmission following the International Physiological Congress in Montreal; this was probably the last occasion when all these notables met at one spot. The neurohumoral theory of synaptic and neuroeffector transmission , at one time hotly disputed ("soup versus sparks"), is now generally accepted. Its origin can be traced back to Galen, who in approximately a.D. 200 stated that the brain releases humors that produce effects on distant organs. It was put in more concrete terms by the German (in spite of his name) physiologist, E. Du Bois-Reymond, a little over a century ago; he proposed that nerves might transmit their impulses across synapses either by electric currents or by the release of chemical substances. The concerted efforts of a great number of people over the succeeding years resulted in overwhelming acceptance of the latter alternative . It is frequently overlooked that an observation that contributed directly to the establishment of the theory had been made earlier by the great French physiologist Claude Bernard. In 1856 he published his classical experiments that demonstrated that the South American arrow poison, curare, paralyzes skeletal muscle by blocking the transmission of impulses at the neuromuscularjunction. He thus showed that the mechanism for the passage of impulses across neuroeffectorjunctions differs significantly from that of their conduction along nerve or muscle fibers. (By hindsight, it is easy to reason that if an exogenous chemical produces a block, it probably does so by interfering with the action of an endogenous excitatory one. This is somewhat analogous to the reasoning that led to the isolation of the endogenous opioids, the endorphins and enkephalins , over a century later, following...