A new conception of the pathology of polyneuritis and other "deficiency" diseases was introduced by McCarrison (20). The most striking manifestations of beri-beri are the loss of the coordinating powers of the muscles. The onset of the disease is generally preceded by the bird sitting with ruffled feathers, and with the appearance of illness. There is progressive weakness, and when disturbed there is a tendency for many pigeons to be taken with convulsive seizures in which they turn "cart-wheels" backwards at intervals until they die. In the acute type of the disease, many birds sit with the head greatly retracted. These symptoms generally led investigators to the acceptance of the view that the lesions in beri-beri were principally situated in the nervous system. The studies of McCarrison, however, reveal the fact that injury to the nerves is much less pronounced than injury to certain other tissues.

On examining pigeons restricted to a diet of polished and auto-claved rice, McCarrison observed functional and degenerative changes in every tissue of the body. The thymus, testicles, spleen, ovary, pancreas, heart, liver, kidneys, stomach, thyroid and brain underwent atrophy, the severity in his cases being in the order named. The adrenals suffered hypertrophy. This hypertrophy was associated with a proportionate increase in the content of the glands in adrenalin. Edema, he found to be invariably associated with hypertrophy of the adrenal glands. In other words edema seemed to be associated with an excessive production of adrenalin.

Inanition was found to give rise to a state of adrenal hypertrophy and to atrophy of other organs, the brain excepted, similar to that observed in birds fed solely upon polished rice, a diet deficient in all known uncharacterized food substances, very deficient in protein and in several essential inorganic elements.

More serious than nerve lesions were the gastric, intestinal, biliary and pancreatic disorders observed in birds as the result of a diet deficient in those factors inadequate in polished rice. Such deficient dietaries gave rise to congestive and atrophic changes in all the coats of the intestine, especially the duodenum; to lesions in its neuro-muscular mechanism; to impairment of its digestive and assimilative functions, and to failure of its protective resources against bacterial infection. In guinea pigs restricted to a diet of oats and autoclaved milk, there were observed lesions of the digestive tract analogous to those seen in pigeons whose diet was limited to polished rice. Owing to the multiple deficiencies of the rice diet, it is not possible to decide from these experiments as to the specific effects of deficiency or absolute lack of a single dietary component. It is suggestive, however, that on a diet deficient only in respect to the antiscorbutic substance, guinea pigs developed lesions, comparable with those found in birds with diets faulty in several respects.

McCarrison (20) further studied upon pigeons the effects of a diet of polished rice, butter fat and onions. This diet was deficient only in the anti-neuritic substance and in several mineral elements, especially calcium, phosphorus, sodium, chlorin and potassium. The iodin in the thyroid was probably sufficient to tide the birds over the periods covered by his experiments. The butter fat supplied the factor A; onions the factor C, the anti-ophthalmic and anti-scorbutic substances respectively. On this diet typical symptoms of polyneuritis promptly appeared, showing that onion does not contain appreciable amounts of the anti-neuritic principle. The addition of onion, of which the birds ate greedily, to polished rice, of which they ate sparingly, afforded some measure of protection against the damaging effects of a diet of polished rice alone, for atrophy of the bowel, although often considerable, was usually less marked than in birds on the rice diet alone. Congestion was less prominent, and the atrophy of the myenteron and of the elements of the mucosa, although usually considerable, were often comparatively slight. Two cases in twelve birds examined were encountered in which bacterial infection of the bowel wall had assisted in inducing profound deterioration of its structures.

In a considerable number of birds whose vitality was depleted as the result of the types of faulty diets described by McCarrison, the blood was found to be infected by Bacillus suipestifer, Bacillus pyocyaneus, or another organism not identified. He pointed out that systemic infection was rendered easier by the presence of the pathological processes existing in the intestine as the result of dietary deficiencies. Such invasion of the body was favored by the impaired production of digestive juices, by the malnutrition of the secretory cells owing to the continued congestion of the mucous membrane, by the increased leucocytic traffic in microorganisms between the mucous membrane of the intestine and the blood, by the greater opportunity which the debilitated mucous membrane provided for the growth of microorganisms on its surface and within its substance, and to actual breaches of continuity in the walls of the bowel itself. The imperfect digestion of food in the upper part of the alimentary tract offering a favorable medium for the growth of bacteria, tended, by the production of unwholesome products, to further debilitate the mucosa, and to increase the prospects of invasion of the latter by microorganisms. In his experimental animals kept on diets deficient in several factors, among which a lack of the anti-neuritic substance was a prominent feature, McCarrison observed with comparative frequency the superaddition of intense bacterial invasion of the bowel walls upon the atrophic and congestive changes brought about directly by malnutrition. Infection of the blood from the bowel under such conditions would be expected and was repeatedly demonstrated by aerobic culture of the heart blood.

In guinea pigs restricted for a time to a diet of oats and auto-claved milk, McCarrison also observed localized, destructive changes in the mucous and underlying coats of the stomach and duodenum. These changes were manifest before the animals had developed any of the characteristic naked eye appearances of scurvy, and he regarded them as pre-scorbutic.