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THE PATHOGENESIS OF RHEUMATIC FEVER—A CONCEPT ALVINF. COBURN, M.D.* Those who refuse to go beyond fact rarely get as far as fact; and anyone who has studied the hbtory ofscience knows that almost every great step therein has been made by the "anticipation ofnature," that, by the invention ofa hypothesb which, though verifiable, often had little foundation to start with; and not infrequently, in spite ofa long career ofusefulness, turned out to be wholly erroneous in the long run. Thomas Henry Huxley I.fustification This is an exposition ofa "hunch." Since it is not a review, observations ofothers will be used for the purpose ofthe argument without reference to an extensive literature. It is not expected that the speculative ideas presented will be convincing; nevertheless, it is hoped that a new approach to an old disease problem may be provocative. The evidence, neither confirmed nor unconfirmed, is mostly circumstantial. No significant relationships are established; this is a recording ofwhat may be concurrent associations . The hypothesis is that lipids protect against activity ofthe rheumatic process. The favorable effect with which this hypothesis deals is that the essential lipid requirements may be attained through diets in infancy and childhood. Moreover, the concept that lipids have a protective role is now ofmore than academic interest; gas chromatography has developed to a degree that the hypothesis can be tested. False or true, the very testing ofthe idea will open new vistas in lipid physiology. Furthermore, as stated byWilliam Trotter: "In science the primary duty ofideas is to be useful and interesting even more than to be true." * Associate Professor ofPediatrics, New York Medical College, New York City. Thb paper was delivered as a lecture September 27, i960, at St. Bartholomew's Hospital, London. Submitted for publication October, i960. Author's present address: Milford Road, Scarborough, Tobago, West Indies. 493 The solution ofmedical problems, like the rheumatic mechanism, may depend on new machines and new techniques—for example, gas chromatography [i]. But this does not mean that creativity in the biological sciences will necessarily stem from new inventions. In the case ofthe physical sciences, it is stated that "most natural phenomena, at all events ofthe inanimate world, have been pretty fully scrutinized" [2]. Emphasis is placed on "the importance of new methods as an aid to creative ideas." This may be true for the inanimate, but medicine is peculiarly animate. It is need that spawns concepts, and it is creative ideas that seek new tools and new techniques. Furthermore, unlike the physicist or chemist, the medical investigator cannot place his reasoning on a purely abstract plane. Furthermore, he must lean heavily on intuition. It now seems clear that a relatively new method, gas chromatography, may permit an attack on the role oflipids at a point where rheumatic fever research has long been stymied. Nevertheless, the successful application ofthis technique to obtain critical information will depend on intuitive planning. It will require that essential "mark" whichwas described bythe late president ofHarvard, A. Lawrence Lowell: "The mark ofan educated man is the ability to make a reasoned guess on the basis ofinsufficient information." Insufficient information is the hallmark of rheumatic fever research. Lord Adrian [2] points out thatthe prescription for the physical sciences may not be applicable to diseases "like rheumatoid arthritis or disseminated sclerosis." He states: "We have to study a complex situation which is continually altering in directions beyond our control." This is true of most disease problems, and it is this continual shifting ofthe many variables in rheumatic fever that attracts the adventuresome explorer. It is this adventuring on one's own into the unknown that has lured the original mind into this unpromising area of medical research. On the encouraging side ofthe ledger is the fact that most ofmedicine's advances have come from adventuresome minds of this character, from uncommitted investigators with worries, with needs, with inspired guesses, with "hunches," and finally with the birth of germinal ideas that have proved revolutionary. Few of medicine's revolutionary changes have evolved from systematic analyses, or from any rational processes, or even from the customary, logical pknning. The greatest advances have been unpredictable. They have come from men intrigued by some unusual...

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