Sicard, Roger and Rimbaud 34 point out that the cerebellar symptoms common in polyneuritis of fowls are not seen in human beriberi, and for that reason they are inclined to doubt whether the avian polyneuritis is actually identical with human beriberi.

The same general condition may be induced in swine,35 rats,36 dogs and cats.37 According to McCarrison,38 although a diet of auto-claved milled rice is fatal to monkeys, these animals die without developing the typical symptoms of polyneuritis, but Gibsdn39 reports that of three monkeys fed on a mixture of white rice, with the addition of sufficient salt mixture to make up for the mineral deficiencies of the rice, one developed typical symptoms of beriberi, while the other two lost weight and suffered from malnutrition, but without neuritic symptoms.

34 Sicard, Roger and Rimbaud, Par. Med. Dec. 1, 1017.

35 Hart and McCollum, J. Biol. Chem. 19, 373, 1914; Hart, Halpin, and McCollum, lb., 29, 66, 1917; Rommel and Vedder, J. Ag. Res. 5, 489, 1915; J. Ind. Eng. Chem. 8, 199, 1916; De Lacerda, Beri. klin. Wechnschr. 23, 159.

36 Steenbock, Kent and Gross, J. Biol. Chem. 35, 61, 1918; Rmmett and Allen, Proc. Soc. Biol. Chem. J. Biol. Chem. 41, liii, 1920.

37 Karr, J. Biol. Chem. 44, 277, 1920; Voegtlin and Lake, Am. J. Physiol. 47, 558, 1918.

38 See p. 173.

39 Gibson, Phil. J. Sci. SB, 351, 1913-14.

Voegtlin and Lake40 describe the following symptoms produced in cats and dogs by an exclusive diet of lean beef heated for three hours at 120° C. in the presence of alkali: Diminution of appetite, constipation, loss of body weight, weakness and sometimes drowsiness, followed by paralytic symptoms, tonic convulsions, spasticity of certain groups of muscles and disturbances of the circulation and respiration.

More recently, Karr41 induced severe polyneuritis in dogs by feeding them vitamin-free diets of casein, sucrose, lard, bone ash and salt mixture. The symptoms induced were comparable with those observed by Voegtlin and Lake. The animals first vomited, became inactive and refused their food, then lost the power of walking or even standing. There were often tremors and twitching, with the head in motion, and occasionally severe tetanic convulsions.42

Weill and Mouriquand 43 report that in addition to the acute form of polyneuritis which develops in fowls after 20 to 25 days there is a chronic form which develops more slowly and which may be produced by a diet consisting of a mixture of raw and sterilized cereals (barley, corn and rice). The chronic condition was characterized by initial paralysis of the wing followed in some cases by paralysis of the feet. These symptoms were associated in certain instances with degeneration of the bones. The symptoms did not disappear when the sterilized cereal in the ration was replaced by raw cereal, nor did they yield to therapeutic administration of the portions of the cereals containing the antineuritic vitamin. In the acute experimental polyneuritis recovery was observed within a few hours after ingestion of raw cereal, bran or injection of vitamin. The investigators conclude that in the acute form the paralysis was due solely to a disturbance of the nerve centers which is chemical in its nature, whereas the chronic form appeared to be dependent on profound nerve degeneration. The paralysis was "functional" in the former case, and "lesional" in the latter. These observations are confirmed by La-picque from his own experiments with mice.

Suguira's observations 44 that extracts of fresh carrots and the crystalline preparations from yeast may cure polyneuritis in those cases where the disease has developed quickly (in about 20 days), while these substances were powerless in cases where the symptoms came on slowly, might also be interpreted as indicating two distinct types of disease.45

40 Voegtlin and Lake, Am. J. Physiol. 47, 558, 1918.

41 Karr, J. Biol. Chem. 44, 277, 1921.

42 For further details of the effect of neuritis-producing diets see p. 171 and ff. 43 Weill and Mouriquand, C. r. soc. biol. 81, 432, 1918. 44 Suguira, J. Biol. Chem. 95, 196, 1918.

As has been pointed out above, the earliest theory of the origin of beriberi was that of an infection. This theory passed into general disrepute as the relation between the disease and the diet was clearly demonstrated by the work of many investigators. Moreover, all efforts to transmit the disease from a polyneuritic animal to a healthy animal on normal diet or to trace the spread of infection from sick to healthy have failed.46 Nevertheless there are still a few adherents of the infection theory. Wydooghe47 describes an epidemic occurring in the African valley of Lukuga in which certain areas or. centres of infection appeared to exist. Alteration in the diet in these centres did not cut short the epidemics, and the diet is said to have been practically uniform throughout the region at all seasons, in spite of which the disease was strictly localised and periodic. Also, outbreaks occurred apparently as the result of camping on old grounds which had previously been marked beriberi centres. Wydooghe believes the disease is due to an infecting germ which is possibly carried by some insect agent, and which is present in the blood for a short period only, so that the propagation of the disease is difficult outside of the epidemic centres and where the carrier is absent.

Barbc 48 likewise finds a purely dietetic hypothesis unsatisfactory, and is inclined to attribute the disease to a microbic infection, possibly involving the duodenal passages, which is favored by an intoxication derived from the food and by unhygienic surroundings. Sprawson 49 believes that the conditions known as beriberi may arise from different causes under different circumstances, the clinical appearance being approximately the same in all cases. One class of cases is due to a vitamin deficiency, while another appears to result from an infection.50

McCarrison51 endeavored with some apparent success, to isolate an organism which would induce beriberi, but Williams and Johnston 52 failed to confirm his results. He himself concluded that vitamin deficiency was an essential factor in the origin of beriberi, but that such deficiency is so rarely complete as to be the sole agent responsible for it, and infectious and parasitic agents are often important causes determining the onset of the symptoms. Bacterial organisms, of whatever kind, that may be isolated from the blood in human beriberi, may invade the blood and tissues under conditions of dietetic deficiency, and thus convert a state of potential into one of active disease. Since such organisms are not the true cause of the malady they cannot be expected to produce it in inoculation experiments. "They are but weeds which flourish in the soil made ready for them by dietetic deficiency." 52a.

45 See also Williams, J. Biol. Chem. 25, 437, 1016. 46 Breinl, J. Trop. Med. 19,120,1016; Sicard, Roger, and Rimbaud, Paris, Med. Dec. 1, 1017.

47 Wydooghe, Bull. Boo. Path. Exct. March, 1018.

48 Barbe, Arch. Med. et Pharm. Nav. June, 1018.

49 Sprawson, Quart. J. Med. 13, 337, 1020.

50 See also Hopkins, Roy. Boo. Med. Sect. Ther. Phann. Lane. 1010, ii, 070.

51 McCarrison, Ind. J. Med. Res. 2, 360, 1014.

52 Williams and Johnston, Phil. J. Sci. 10B, 337, 1015.