XI. PATHOLOGY 493 



that normal human gastric juice administered to pernicious anemia patients 

 together with crystaUine B12 is followed by a therapeutic response unob- 

 tainable when the vitamin is given without gastric juice''- ''* supports the 

 theory of Castle concerning the role of a gastric secretory product, the 

 intrinsic factor, in the maintenance of normal hemopoiesis.'^ Although a 

 considerable amount of information has been acquired concerning the phys- 

 ical properties of intrinsic factor, it has not been isolated in pure form and 

 little is known of its chemical nature. Recently, its close association with 

 gastric mucoprotein has been demonstrated by Glass and associates.'^ 



The extrinsic factor of Castle has been shown by these clinical experi- 

 ments with gastric juice, as well as by others, in Avhich derivatives of ani- 

 mal duodenal and gastric mucosa were employed,'^- '^ to be vitamin B12 

 or one of its analogs. Furthermore, since B12 alone is effective when ad- 

 ministered parenterally to pernicious anemia patients, the mference is clear 

 that the erythrocyte-maturing factor of liver, postulated by Castle and 

 associates as the product of interaction between intrinsic and extrinsic 

 factors,'^ is also B12, perhaps present in "bound" form, but not altered 

 chemically bj'' its association with intrinsic factor. If this view is correct, 

 and its validity seems to have been well established by studies concerned 

 with the isolation and characterization of B12, as well as by clinical inves- 

 tigations, then it must be concluded that the role of intrinsic factor is to 

 render B12 available for absorption, or to facilitate its absorption from the 

 alimentary tract. 



Progress has been made toward the elucidation of this problem by the 

 demonstration of a binding action of gastric juice and of gastric and in- 

 testinal derivatives on B12. The complex so formed fails to support the 

 growth of organisms, such as mutant strains of E. coli, which require an 

 exogenous source of the vitamin. The protective effect of intrinsic factor 

 on B12 might be exerted in two ways. The vitamin might be spared from 

 utilization by intestinal bacteria, or from inactivation by their products, 

 and in either case become available to the host. Moreover, the presence of 

 free B12 in the proximal portion of the intestine should enable organisms 



i»L. Berk, W. B. Castle, A. D. Welch, R. W. Heinle, R. Anker, and M. Epstein, 



New Engl. Med. J. 239, 911 (1948). 

 >^ B. E. Hall, E. H. Morgan, and D. C. Campbell, Proc. Staff Meetings Mayo Clinic 



24, 99 (1949). 

 IS W. B. Ca.stlo, Science 82, 159 (1935). 

 »« G. B. J. Glass. L. J. Boyd, M. A. Rul)instein, and C. S. Svig;als, Science 115, 101 



(1952). 

 " F. H. Bethell, M. E. Swendseid, M. C. Meyers, R. B. Neligh, and H. G. Richards, 



Univ. Hasp. Bull., Michigan 15, 49 (1949). 

 's B. E. Hall, F. H. Bethell, E. H. Morgan, D. C. Campbell, M. E. Swendseid, S. 



Miller, and A. .\. Cintron-Rivera, Proc. Staff .]fcetings Mayo Clinic 25, 105 (1950). 

 i» W. B. Castle, W. C. Townsend, and C. W. Heath, Am. J. Med. Sci. 180, 305 (1930). 



