An Overlooked Parallel to Kekulgs Dream The Discovery of the Chemical Transmission of Nerve Impulses by Otto Loewi Uhich W e b Laboratory of Chemical Physlcs, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda. MD 20892 Ronald A. Brown The Polytechnic of North London, Holloway, London N7 8DB. England Much controversy has centered recently on the reliahility of KekulB's late (1890) acccount of the dreams that led him t o recognize the abilitv of carbon atoms t o form chains. (1855) and to formulati the structure of benzene (1865166,: This dehate ( 1 ) has aenerated a great deal of interest. The verdicts (2) range from: no reasonto disbelieve (what should the world-famous elderly man have expected t o gain from concoctingsuch afairly implausible story?) to the claim that the illustrious chemist,"in the twilight of his life", had acted from German chauvinism (3a), and the recent surprising assertion that KekulB's account was given "at a beer party . . .when he likely had had one too many" (4). Three distinct topics are a t issue: the trustworthiness of KekulB's account. the auestion of whether scientific ideas can appear in adrkamlide state, and the wider one of the role of intuition and imagination in science. Much of the negative view on the first one of these questions is based on the fact that KekulB had not mentioned these dreams in print (emphasis ours) between their alleged occurrence and 1890. Coupled with this is the denial that nondeductive intuition could play any role in the advancement of science, which is said to be possible exclusively through experimental work to get hard facts first, and the-stern ikjun&iou that chemists must stop dreaming (i.e., having any ideas?) and must "get out from under the KekulB myth" if "they wish to succeed" (3). In view of all these conflicting interpretations, it is surprising that hardly anyone (5),to the best of our knowledge, has mentioned a closelv analoeous instance of a dream with " important scientific consequences, an instance that has manv similarities with KekulB's dreams but that. in contrast, is ns completely documented as such an enti;ely subjective experience can be. We refer to the dream oriain of the discover; of the humoral (i.e., chemical) transm&ion of nerve impulses (6) in 1921 by Otto Loewi (1873-1961) of Graz, Austria (7). Loewi himself has published two concordant accounts of these events (8a,b). Both of them describe how he awoke in the early morning hours with aclear idea for a crucial experiment to solve a fundamental problem of neurovhvsioloev1--a vrohlem. incidentallv. in which he was ." not consciously interested a t that t i m e . 2 6 jotted down the brilliant thoueht and went back t o sleev. The next dav he remembered that he had had a most important idea the vinht before but was quite unable to recall durine that "most desperate day in my whole scientific life7'@)what that idea
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had been or to decipher the hasty notes he had made. The idea did, however, recur the next night; this time, Loewi did not take anv risk. aot uv a t once in the small hours of the morning, walked t h e few blocks t o his Institute, and performed the "simvle exoeriment" (86). When his co-workers arrived a t 8:00 a.m., the normal starting time, the work had been successfullv completed. As in ~ekulB'scase,-the story of his dream was committed to print b y Loewi himself only years later," hut this cannot b e a n obstacle to its acceptance: a background incident of this kind would have been considered out of place in a sober, factual account of serious scientific research in KekulB's or Loewi's time just as much as in our own. Can anyone visualize rettine such a storv vast the referee of anv orimarv jouka?? However, ~ o e wGas i very fond of telling a b u t the& events. and he willinelv comvlied with the freauent requests to do so. One of u$ has orten heard the s&ry from him during a period of more than 20 years (1938-1961) and can testify that i t was always told in essentially the same way, without major variations. The same fact is stressed by Loewi's lifelong friend, Henry H. Dale, in his memorial trihute to Loewi (9). Even more significant: Loewi's daughters clearly recalls to this day how her father told her about his -
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'This brief note in a chemical journal is hardly the place for a
detailed explanation of the problem of neurophysiology that was solved through the experiment suggested to Loewi in his dream. Briefly, the question answered had to do with the mechanism by which the two branches ol the so-called vegetative nervous system: the vagus and the sympathicus, respectively, act-often in mutually antagonistic ways-upon the organs they influence. The heartbeat. for instance, is slowed down by action of the vaous, sped up by that of the sympathicus. These effects had long been thought to occw through electric currents, but Loewi's experiment,using frogs'hearts, proved that release of chemical substances is actually involved: acetylcholine from the vagus, adrenaline from the sympathicus, at least in the frog. Interesting comments on this point are Qiven in Loewi's last purely scientific paper (12). Actually, an account of Loewi's dream has appeared in print in a book by Cannon (13)several years before the publication of ref. 8a. Cannon, a close. admired (8b)friend, must have heard the story being told by Loewi; he cannot have failed to secure permission for including it in his book.
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Mrs. U. W.
dreams and their conseauences on the dav after these of information often repeated events. She also adds a verbally by Loewi later on but omitted from his published account (presumably as not being significant enough to get into print): that his co-workers, when they arrived in the labor&ory that day, predicted that that morning's results would get him a Nobel prize. T o his daughter, he added: "Wouldn't that be something?" The prediction was fulfilled when Loewi and Dale shared a Nobel Prize in Medicine or Physiology in 1936. To reassure those who insist that hard work in the laboratory gathering data, with subsequent interpretation, is the only possible, indeed the only permissible way to scientific progress, we may add that for Loewi and his associates the years 1921-1938 were filled with intense experimental work to secure the results of the first experiment, to explore its further consequences, to identify the chemical agents that had been proven to be involved,' and to develop the field of neurohio~hemistr~ based on these results. he enormous importance of this field is too well known to need special comment. This work was documented in a series of 14 major papers, until nonscientific events put an end to these studies 186).
w e feel that the story of the background of Loewi's discovery proves quite conclusively that ideas for highly significant scientific research can indeed appear during sleep, as Kekulb had related. The doubts raised against such a possibilitv are not valid. The veracity of the great founder- of structural
organic chemistry need not be questioned. His delay in getting his story into print cannot possibly he held against him. Cases of this kind do not seem to be all that exceptional. While writine this note. we came across a number of examples, including a statemknt by Hermann von Helmholtz (10) that fruitful ideas " often. . .came in the morning upon waking. . . , a s Gauss also noted". We feel that the story to which we wish to call the attention of our fellow chemists proves the validity and wisdom of KekulB's often-quoted remark (11):"Let us dream, Gentlemen, then perhaps we shall find the truth. . .but let us beware of publishing our dreams till they have been tested by the waking understanding.'' Literature Clted
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Se1tzer.R.J. Chem.Ena.Neu8 1985. (Nov 41.22 and literature quoted there. 2. Rarnsay.0. B.:Roeke,A. J. Cham. Brit. 1984,20,1093. 3. Ial Wotiz, J. H.; Rudovrky, S. Chem. Blii. 1984.20. 720; Ihl Chem. Enp. News 1986, us". 20). 3. 4. (a1 Vanderbilt. B.M. J. Chem. Educ. 1975.62;Ihl Chem. Eng.Nei.8 1986, (Feb. 24j.4. 5. For an exception, see Brown, R.A : Luckcock. R. G. J . Chem. Educ. 1918 5.694. 6. Loswi, 0. Pflfip~r'sArehi" /d.peaomt~Physiol. 1921,169, 239. 7. A" interesting account of Loewl'a life, pernonsiity, and research is given in: Lernheck, F.:Giere.Mi. DtioLosmi.EinLebrnrbildin Dakumsnten:S~~inxer-Ver1aa:Berlin. 1968. 8. (a1 Loewi, 0. Fmm the Workshop of Disrooev, Porter Lectures, Series 19,University of Kansas: Lawrenee. KS, 1953: p 20. Ibl Loewi, 0. An Autobioprophic Shalch. Pmpeef. B i d Med. 1960.4.3. 9. Dale. H. H. B i d Mem. Fell. Roy. Sac. 1962.8.67-69. 10. Sepe.E. From FollinpBodias foRodio Woues: W . H . Froeman: New York,1985;p 2% Cf, g 61 in Cannon, W . B. in ref. 13. 11. Schultz, G. Ber.drut. Chem. C P S 1890,23, . 1265. 12. Loowi.0. J . ML.SinoiHosp. 1957.24.1014. 13. Cannon, W. B.The Woy of on Inuestipalor: Norton: New York, 1945; pp M.61. 1. See the account ofthecontrovenv bv
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