Anti-Pernicious Anæmia Factor

Abstract

TWENTY-TWO years ago, Minot and Murphy postulated the presence in liver of a factor effective against pernicious anaemia, and many attempts at its isolation have been made. The long quest now seems to be nearing its end with the independent appearance within a week of two papers, from the United States and Britain, announcing the isolation of red substances having extremely high potency. The American workers (E. L. Rickes, N. G. Brink, F. R. Koniuszy, T. R. Wood and K. Folkers, Science, 107, 396 ; 1948) describe crystalline material effective in a single dose of some 15 µgm., that is, with roughly two thousand times the haematopoietic potency of folic acid. Dr. Lester Smith (Nature, 161, 638 ; April 24, 1948) does not appear to have taken the purification so far but has separated two different red pigments, both clinically active. These may turn out to be peptide conjugates of this crystalline substance. He gives more information about the properties of his materials than do the Americans, including a value of approximately 3,000 for the molecular weight. The Americans were assisted in their fractionation by a microbiological assay method using L. lactis Dorner. The British work depended on clinical assays, of which more than eighty were carried out, and on the red colour. It also established the important fact that the highly purified red material, unlike folic acid, is effective against subacute combined degeneration of the spinal cord. The crystalline substance, for which the Americans suggest the rather unsatisfactory name ‘vitamin Bl2', is remarkably potent, being effective at a daily dose of about 1 µgm. only. A rough calculation indicates that it would require at least twenty tons of liver to yield 1 gm. of crystals. This is in itself sufficient explanation of the fact that these advances have come not from academic institutions but from two industrial laboratories, namely, those of Merck and Co., Inc., Rahway, New Jersey, and Glaxo Laboratories, Ltd., Greenford, Middlesex.