Shibayama 53 came to somewhat the same point of view from his study of beriberi in Japan. While a monotonous and one-sided diet may give rise to the onset of the symptoms, he is unwilling to grant that this is the true cause of the disease. The symptoms and anatomical changes seem to him to develop from intoxication by a poison which is produced by a certain micro-organism in the body, especially in the intestine.

Lebredo 54 has reported experiments which demonstrate the existence of an extremely persistent bacterial organism which he believes may be responsible for the production of a " beriberi toxin," but these experiments also lack confirmation at present.

The early investigators who studied the connection between beriberi and a polished rice diet, noting the resemblance between the polyneuritic symptoms and those of an intoxication, reached the conclusion that polished rice contained some toxin either inherent in the rice or produced by the action of moisture or a fungus growth.55 It has been frequently demonstrated, however, that the onset of the disease is not dependent in any way upon the use of spoiled or fermented rice, and the theory of a toxic substance naturally present in the rice grain was entirely disproved by the work of McCollum and Davis," who showed that on the one hand substitution of dextrin or purified casein for half the ration of polished rice caused no improvement in the condition of rats who had begun to decline on a diet of rice alone, and, on the other hand, no toxic effect was produced by the inclusion of as much as 80 to 90 per cent of polished rice in the diet, provided egg, milk powder, or wheat embryo were fed at the same time.

52a Clair (Bull. soc. pathol. expt. 13, 191, 1920) claims the conditions produced in pigeons by feeding with polished rice have no connection with beriberi. In human beings the disease is alleged to be due to toxic products of bacterial decomposition of rice. It is thus regarded as an infectious disease, though the agent has not yet been isolated.

53 Shibayama, J. Trap. Med. Hyg. 16, 283, 1914.

54 Lebredo, Proc. 2nd, Pan. Am. Sci. Cong. Sect. 8, pt. 2, p. 29.

55 Braddon, "The Cause and Prevention of Beriberi," 1907; Couzien, Ann. hyg. med. colon. 16, 445; Zentr. Bioch. Biophys. 14, 909; Caspari and Moskow-ski, Berl. klin. Wchnschr. 1913, 1, ii, 1515; Williams and Johnston, Phil. J. Sci. 10B, 337. 1915; Goto and Takahata Choo, Igaku-Zaashi, 25, 575, 1918, quoted by Ixrane, J. Tok. Chem. Soc. 41, 225, 1920.

56 McCollum and Davit, J. Biol. Chem. 23, 181, 1915.

A variation of this theory of intoxication is found in the hypothesis of Walshe,57 who believes that there are two factors responsible for beriberi, one of which is vitamin deficiency and the other an intoxication due to the abnormal hydrolysis of carbohydrates with the formation of toxic products. According to Walshe the beneficial effect of the rice polishings and similar curative substances is due to the vitamins present which play some undetermined role in regulating the carbohydrate hydrolysis, while the earlier intoxication theories assume the presence of some substance in the bran which neutralised the toxins of the rice.

Schaumann 58 noted an abnormality in the phosphoric acid content of the urine of beriberi patients, and concluded that beriberi was connected with faulty phosphorus metabolism, a view with which Mos-kowski 59 is in accord.59a The evidence on which this view is based is, however, capable of another interpretation.60

In 1911, Funk took up the study of the disease and developed his vitamin theory according to which beriberi and polyneuritis are caused by deficiency of vitamin B.61

57 Walshe, Quart. J. Med. 11, 320, 1018.

58 Schauman, Arch. Schiib-u-Tropenhyg. 12, 683; Chem. Zentr. 1908, ii, 1066.

59 Moskowski, Arch. Schiffs-u. Tropenhyg. 15, 653, 1912-13.

59a The belief that in the absence of vitamin B and the subsequent development of beriberi there is a breakdown in metabolism, more particularly in regard to the metabolism of carbohydrates, has led Findlay (Biochem. J. 15, 104, 1921) to determine the glyoxylase content of the liver in avian beriberi; for glyoxylase plays an important part in carbohydrate metabolism. The results obtained suggest that in pigeons suffering from beriberi there is, as compared to control birds, a reduction in the glyozalase content of the liver. The administration of vitamin B produces a definite increase in the amount of glyoxylase.

60 See p. 79 on the relation between vitamin and P3O5 contents in grains.

61 Funk and Cooper, Lane. 1911, ii, 1266; Funk, Trans. 80c. Trop. Med. 5, 86,1911; J. Physiol. 43, 395. 1911; Ib, 44, 50; lb., 45, 75, 489, 1912; /6, 46, 173; Proo. Physiol. Soc. J. Physiol. 47, xxv., J. Physiol. 48, 228, 1914; lb., 53, 247, 1919-20; Funk and von Schonbora, Jo., 48, 328, 1914; Funk and Douglas, J. Physiol. 47,475; Funk, Ergebniss. d. Physiol. 13,125,1912; Z. physiol. Chem. 88, 352,1912; 89, 373, 378, 1913; J. State Med. 20, 341, 1913; Parm. J. 89, 351; Brit. Med. J. 1913, i. 814; Bioch. J. 7, 81, 211, 1913; Funk and Macallum, 7b, 7.