Toxic protein derivatives causing aplastic anemia; a review.

I N June, 1957, L. L. McKinney and associates reported the climax of a prolonged study of fundamental biologic and medical interest, the synthesis of S( dichlorovinyl ) -L-cysteine, a compound which upon oral administration to calves in doses of only 10 mg./100 lbs. daily, produced a fatal aplastic anemia similar to that produced by feeding trichboroethylene-extracted soybean oil meal.1 As early as 1916, Stockman associated a severe hemorrhagic disease in cattle, which broke out in south Scotland, with feeding on soybean meal after extraction of the oil with trichboroethylene.2 The soya bean, long an important article of human food in the East, was becoming more widely used in the feeding of cattle. The bean was too rich in oil to serve as a good stock food, and, moreover, the oil was far more valuable for other purposes. Soya meal which had been extracted with naptha had become highly regarded by animal growers. In the Scotland outbreak, 67 cows on 9 different farms had become ill. Fifty-four of these died and 13 recovered. The cattle owners attributed the trouble to the feeding of a new consignment of soya bean meal or cake. Investigation with the manufacturer revealed that the appearance of the cattle disease synchronized with the replacement of naphtha by trichloroethylene as the extracting solvent. Stockman was abbe to reproduce the disease experimentally by feeding trichloroethybene extracted meal to cattle. Many cases of the disease were subsequently observed in Germany and Holland in 1923 and 1925, and later in different areas of the United States, Hawaii and Japan.3 In the late winter and spring of 1951 an oumtbreak of fatal aplastic anemia occurred in Minnesota dairy cattle. Field studies showed that all of the involved animals were in herds that had been fed, as part of their ration, tnchloroethybene-extracted soybean oil meal (TCESOM ) . Two extraction plants using this solvent combined with a heating process had begun operation a few months earlier. Calves under six months of age, the most highly bred, best-producing milk cows and those late in pregnancy were particularly susceptible. Those fed the greatest amount of TCESOM were affected first and most severely. Unconfirmed reports appeared in one area that several persons who had consumed milk from cows fed TCESOM developed a hemorrhagic disease. A systematic study of the relationship of bovine aplastic anemia to TCESOM was undertaken by M. 0. Schubtze and collaborators at the Minnesota Agri-