A golden anniversary: cattle twins and immune tolerance.

0 CCASIONALLY a chance observation jump-starts a whole field of science. The discovery of immune tolerance and the recognition of self and nonself is such an event. It started with a 1944 letter from a cattle breeder in Maryland to the University of Wisconsin immunogenetics laboratory, reporting a curious pair of twin calves, unusual in having different fathers. RAY OWEN, a postdoctoral fellow in the laboratory and already interested in blood groups of cattle twins, thought they would provide an interesting opportunity for blood group analysis, so blood samples were sent to him. In the thirties and forties, the genetics of blood cell antigens was an active field for investigation. It was then a popular view among geneticists that antigens, because of their simple inheritance, might be immediate gene products. For this reason, they might provide an insight into the nature of that maddeningly elusive entity, the gene. In pursuit of this possibility, new blood types were actively sought in various species, including Homo supiens and Bos taurus. By the early 1940s, 40 different antigenic specificities had been identified in cattle. The world leader in cattle blood groups was the immunogenetics laboratory at the University of Wisconsin, founded by L. J. COLE and M. R. IRWIN (OWEN 1989). There was sometimes uncertainty about paternity in cattle, and when valuable animals were involved, that could be an important economic issue. Breeders and breed associations welcomed blood groups as a foolproof way of identifjmg sires. The immunogenetics laboratory provided valuable information and the breed associations provided financial support, vitally important in those pre-NIH/NSF days. It was a win-win situation. The events that led to the letter involved a Guernsey cow with twin calves. She had been properly mated to a Guernsey bull, but shortly afterward a lustful Hereford escaped from a neighboring area and got into the act. The color patterns of the calves showed clearly that the twins had different fathers. Blood analysis revealed that the COW carried (among many others) antigen G. The Guernsey bull had antigens S and X2, while the Hereford bull had R and 1’.