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Willenegger 1965), no work had been published dealing with the wear or corrosion products to be expected from total joint replacement prostheses.

IT has been shown in this laboratory that malignant tumours, mostly rhabdomyosarcomata, are readily induced in rat skeletal muscle by implants of powdered metallic cobalt (Heath, 1956).In histogenetic studies of these cobalt-induced tumours (Heath, 1960) the stages of initial muscle damage followed by regeneration and attempts at repair are clearly defined, and the emergence of abnormal and later malignant myoblasts, can readily be followed. It is reasonable to suppose that the free myoblasts takilng part in the regeneration process are subject to a concentration gradient of dissolved cobalt. Initially, it was assumed that this metal was probably in the ionic form, since it was observed that the metal slowly disappeared from the injection site by some process other than phagocvtosis.As cells in culture usually respond to an experimental agent in much the same way as cells in vivo, experiments were made in which cultures of rat myoblasts and fibroblasts were treated with cobalt chloride in various concentrations, in the hope of reproducing in vitro the premalignant changes observed in vivo. The results were disappointing, however. At concentrations above a certain level, the cells were killed; at sublethal concentrations they appeared unaffected, and showe(d no cytological abnormalities like those in the early muscle tumours.From these negative results, together with additional evidence (unpublished experiments) that, at least in suspensions of mouse ascites cells and rat dermal fibroblasts, ionic cobalt was bound mainly at the cell surface and was not incorporated intracellularly, it seemed unlikely that ionic cobalt was the carcinogenic agent in vivo as originally supposed. Since a period of several weeks elapses between the implantation of the metal and the first appearance of the premalignant cytological changes, it seemed possible that the metallic cobalt might slowly interact with a tissue component and that the complex thus produced might be the carcinogenic factor. It was thought that such a complex might be more e Asily taken up by the cell than ionic Co2+; its subsequent breakdown by intracellular enzymes might then liberate cobalt into susceptible regions and thus initiate the malignant changes.The results (lescribed in this paper show that powdered metallic cobalt dissolves slowly when incubated aseptically with horse serum, to yield a solution of characteristic colour in which much of the dissolved metal is bound to protein. Not only is the cobalt in this form less toxic to rat myoblasts in culture than the equivalent concentration of CoC12, but also it produces in actively growing cultures (containing many dividing cells) cytological alterations similar to those seen in the premalignant myoblasts in vivo.