The secondary etiologic factors are mainly predisposing; a few words, however, must be added concerning what may be termed _exciting factors_. Infection is the most important condition which may suddenly and precipitously induce scurvy. This fact was brought to our attention in 1912 in connection with the outbreak of scurvy among infants receiving pasteurized milk. Its explanation was not clear at the time, but was elucidated by subsequent experience, and was described in 1917 as follows: "Latent scurvy was prematurely changed to florid scurvy by the presence of a ward infection; an epidemic of 'grippe' precipitated an epidemic of scurvy exceptional in its hemorrhagic tendency." The association of scurvy and infection has been recently emphasized by McCarrison and others, and seems to hold good for the other so-called deficiency diseases. In this connection one other exciting cause of scurvy may be mentioned, namely, trauma. The older writers noticed that following a fall or an accident, a sailor frequently developed scurvy, and Barlow in 1894 remarked on the influence of trauma in connection with infantile scurvy. As might be inferred, its effect is mainly to induce premature rupture of the weakened blood-vessels; in infants we have seen this occasioned by pressure exerted on the lower end of the thigh to ascertain the presence of tenderness. Viewing the situation broadly, it must be acknowledged that except for the realization that scurvy is due to a new food factor--a vitamine--our fundamental understanding of its pathogenesis has advanced but little, in spite of the employment of experimental methods and the availability of modern technic. It is doubtful whether mere clinical studies will contribute in a large measure to the solution of the pathogenesis of scurvy. Much may, however, be learned by investigations of the metabolism in human scurvy--an aspect of the problem which, as will be brought out in a subsequent chapter, hardly has been explored. By this means may be acquired a clearer understanding of the effect of an antiscorbutic deficiency on the tissues and on cellular activity. Much may be expected from physiologic and pharmacologic studies of the specific vitamine, although it is not yet available in a pure state. Finally, it is probable that the solution of similar questions relating to the pathogenesis of cognate disorders--a study which is engaging the best efforts of so many workers throughout the world--will shed light on this particular disease. CHAPTER III THE ANTISCORBUTIC VITAMINE[22] [22] Vitamine is used throughout this monograph as synonymous with "accessory food factor" or "food hormone" as a convenient descriptive term, without any intention of connoting a definite chemical substance.