My early experience with bishydroxycoumarin (dicumarol).

IN THE LAST of March 1941, my associate at the Mayo Clinic, Dr. H. R. Butt, gave a lecture at the weekly meeting of the staff of the 1\layo Clinic on the use of vitamin K to correct deficiency of prothrombin associated with jaundice and disease of the liver. In the course of that lecture he mentioned a comI)ound that had been prepared which was capable of producing a deficiency of prothrombin in animals. This state apparently could not be corrected by the administration of vitamin K. After the lecture I asked Dr. Butt about the new preparation, and found that he had read about it only a feew days previously in the Joarnial of Biological Chemistry. The work had been done by Dr. Karl P. Link and his associates at the University of Wisconsin. Dr. Butt had been working with vitamin K and measurements of prothronibin for several years, and he was greatlv interested in this new discovery. A request was sent to Dr. Link for a supply of some material for clinical use. We discussed at some length the possible clinical uses of this material but, to the best of our knowledge, it never had been administered to a human beimig, so all we could do was to speculate. We did have high hopes. Dr. Link and his associates very promptly sent to us some bishydroxy-coumarin (Dieumarol). A study of the effect of this (ompoulnd on dogs was begun by Dr. J. L. Bollman about the middle of April 1941. The results of his studies confirmed the observations of Link alm(l his associates. My associates and I who were interested in nitravaseular (oagulation had used heparin for a number of years. Heparin was knows to be valuable ili the treatment of vascular