Scurvy, Past and Present

by Alfred F. Hess

CHAPTER V
EXPERIMENTAL SCURVY

There is no mention whatsoever of scurvy in animals previous to 1895, when Theobald Smith wrote: “When guinea-pigs are fed with cereal (it has been observed for some years in this laboratory), with bran and oats mixed, without any grass, clover, or succulent vegetable, such as cabbage, a peculiar disease, chiefly recognizable by subcutaneous extravasations of blood, carries them off in from four to eight weeks.” Smith did not pursue the subject further.

Coincident with the appreciation of the value of experimental methods, one would have expected attempts to produce scurvy in animals. The disorder had been recognized for a great many years, the fact that it was occasioned by a dietary deficient in fresh food was widely known, so that it would seem natural for clinicians or laboratory workers to have tried to induce the disease in animals by a similar restricted diet. There is, however, no suggestion of such an experiment in the voluminous literature on scurvy. The explanation of the neglect of an experimental study of scurvy appears to be that this was considered a disorder which required little investigation—its etiology, its prevention and its cure seemed thoroughly understood. It is strange that the mere fact that such a severe disturbance responded, as if by magic, to the administration of simple foodstuffs should not have awakened curiosity as well as wonder, and stimulated inquiry into the nature and significance of the curative agent.

In 1903 Bolle published the results of experiments on guinea-pigs which had been fed for various periods on raw or sterilized milk. He reported that the animals developed a marked fragility of the bones, varying in intensity in proportion to the degree of heat to which the milk had been subjected. These changes Bolle interpreted as typical scurvy, but it is difficult to decide whether the disorder was actually true scurvy, in view of the indefinite description of the bone lesions.

Bartenstein repeated Bolle’s work and described in detail the changes in the bones. From his work we learned that it was of little moment whether the animals were fed raw or sterilized milk—their nutrition failed within about the same length of time, and they died within a month. The chief pathologic change was a marked fragility of the bones, leading to spontaneous fractures, or to breaking of the bones in the course of ordinary manipulation. Bartenstein described the disorder as “beginning with the degeneration of the marrow, and secondarily leading to an atrophy of the bone due to increased absorption and deficient new formation of bone, especially at the endochondral lines of ossification. As the result of the osteoporosis, spontaneous fractures occur without noticeable hemorrhagic diathesis.” He found a deficiency of calcium in the bones of animals suffering from even a mild degree of this disorder. Hart and Lessing are of the opinion that we cannot accept Bartenstein’s diagnosis of scurvy. They compare this disorder to that described by Ziegler as “osteotabes infantum,” in which there is a more or less pronounced “jelly marrow” which has replaced the lymphoid cells in scattered areas. They sum up their analysis of the question with the statement that “the primary marrow changes in the diaphysis, the marked lacunar absorption by osteoclasts, the absence of subperiosteal hemorrhages, do not indicate typical scurvy.” Schmorl produced comparable lesions in dogs and came to the conclusion that the disorder was one “very similar” to scurvy but not identical with it, the essential difference being that in all animals there was a most marked absorption of bone by osteoclasts.

Similar results were obtained by others. In 1904 Peiper and Eichloff attempted to produce scurvy in dogs by means of a diet composed exclusively of raw or of sterilized milk. The following year we find a report by Esser of feeding goats on sterilized milk. None of these studies hits the mark; a condition of fragilitas ossium was produced rather than typical scurvy.

In 1907 the first systematic and convincing experimental study of scurvy appeared. In this year Holst and Froelich published a preliminary account of their classic work, undertaken in an endeavor to fathom the nature of “ship beriberi,” a disorder which disabled so many of the sailors in the Norwegian navy. We must remember that until recently attention has been focussed on the infectious diseases, and little thought given to the investigation of nutritional disorders. Although experimental investigation in this field may be stated to have been initiated by this work, it in turn had been stimulated by a conception of dietary diseases which had just begun to be realized. This new viewpoint was the result of the work of Eijkman. As has been mentioned in considering the pathogenesis of human scurvy, Eijkman demonstrated that hens developed polyneuritis, a disease resembling beriberi, when fed on polished rice, and that the simple change to a diet of unpolished rice, or the addition of rice polishings to the dietary, sufficed to protect or to cure. This work had been repeated and substantiated. It was evident to those who considered the question that the old lines of thought in regard to food and dietetics inadequately explained remarkable phenomena of this kind. It was also clear that nutritional disorders were subject to experimental investigation in a way similar to the infectious diseases, which were absorbing the interest of the various laboratories. It is unnecessary to review the rapid rise of investigative work in this field. It may be stated, in general, that during the past few years the investigations of scurvy have become so numerous that an established research technic may be said to have developed in connection with its study.

Attempts have been made to produce scurvy in various animals, but it has been brought about regularly only in the guinea-pig and in the monkey. Experiments on the dog are as yet too few to justify our regarding this animal as definitely available for this study. The nutrition of rats, mice, rabbits, hogs, pigeons, fowl, receiving a diet identical with that which regularly occasions scurvy in guinea-pigs, either progresses normally or a state of malnutrition develops which cannot be identified with scurvy. Recently Hart, Steenbock and Smith have reported that cattle can be reared to maturity on a diet which will produce scurvy in the guinea-pig in four to five weeks. We are therefore confronted with the remarkable and inexplicable phenomenon, a fact concurred in by almost all investigators, that a diet induces either normal nutrition or malnutrition, according to the experimental animal employed. A diet of polished rice, or other decorticated grain, will lead to the development of scurvy in the guinea-pig, to polyneuritis in the pigeon or fowl, or, according to Holst and Froelich, to a combination of these disorders in the hog.[35] The basis of these divergent results cannot be surmised, and is worthy of the most thorough investigation. It may well be that the elucidation of this problem—for example, why we are able to bring about scurvy in the guinea-pig but not in the rabbit, will shed light on the pathogenesis of this disorder. Are we to conclude that some of these animals have the power to synthesize the vitamine whereas others must depend upon the food for it, or are we to presuppose an ability to maintain normal life and function without any or with a minimal amount of this vitamine? The difference between these two groups, the susceptible and non-susceptible animals, probably is not as absolute as we have been wont to regard it. Recently Harden and Zilva have shown that although rats are able to thrive on a diet free from antiscorbutic vitamine, they show an appreciable gain in weight when this factor is added to the dietary. If such be proved to be the case, we must regard the non-susceptibility of the rat, the rabbit, etc., as relative rather than absolute.

From time to time a doubt has been raised as to whether we should accept guinea-pig scurvy as the counterpart of human scurvy. This question can be answered only by comparing the disorder in the one species with that in the other—as to mode of production, pathology, symptomatology, means of cure and all other phenomena. Viewed from these standpoints it is found that in almost every respect the disorder is identical in man and in the guinea-pig. The outstanding distinction is the difference in the length of time elapsing before the development of symptoms. In the child or in the adult it takes about six months of the deficient diet before clinical symptoms are manifest and a diagnosis can be established; in the guinea-pig the disorder can be recognized two weeks after restricting the diet. In the one instance we seem to be dealing with a nutritional disorder which is chronic or at least subacute, and in the other with a markedly acute condition. This distinction is open, however, to certain qualifications. In the first place, we must consider the duration of life of the two species, the comparatively short span of the guinea-pig compared with that of man. It must be borne in mind, furthermore, that the guinea-pig is placed on a diet absolutely devoid of all antiscorbutic vitamine, whereas this rarely obtains in human beings. For example, the diet which is most markedly scorbutic for infants is the “malt soup” previously mentioned, but even this food contains an amount of the antiscorbutic factor which is not negligible. But after taking these differences into consideration, it is nevertheless evident that the guinea-pig is far more sensitive to scurvy than man. This does not indicate that the guinea-pig is an unsuitable experimental animal, any more than the fact that the pigeon is more susceptible to polyneuritis than man indicates that it is unsuited to investigations of beriberi. It merely prevents our carrying out delicate quantitative experiments, and cautions against drawing too finely-spun deductions. In all nutritional investigations it should never be forgotten that conclusions drawn from experiments on animals are merely provisional, and must await substantiation on man, and, furthermore, that where differences in reaction are noted, the clinical data should be accorded full consideration.