Further observations on the specificity of the folic acid molecule.

BRANDENBURG, M.D.,* AND TOMAS ARAMBURU, M.D. I T HAS been established that pteroylglutamic acid (folic acid) stimulates the development of white blood cells, red blood cells and platelets in a variety of animal species and in persons who have certain types of macrocytic anemia. Our studies of folic acid have been concerned chiefly with the striking hematologic response which follows its administration to persons with pernicious anemia, nutritional macrocytic anemia and tropical sprue in relapse. This response has been described in considerable detail,’ and it has been pointed out that it is indistinguishable from that which follows the administration of refined liver extracts. Nevertheless, the potency of refined liver extracts is out of all proportion to the amount of folic acid they contain, and it is our working hypothesis that the hemopoietic factor in refined liver extracts differs chemically from folic acid per se. The study of the synthetic folic acid molecule offers great promise toward determining something of the nature of blood regeneration. Recently we showed2 that patients who do not show a hematologic response to methyl folic acid will respond to the folic acid molecule. Since this study was reported, we have investigated the hemopoietic properties of six additional compounds, somewhat related to folic acid in their chemical structure, in persons with Addisonian pernicious anemia, nutritional macrocytic anemia and tropical sprue in relapse. This communication is concerned with these extended observations on the specificity of the folic acid molecule.