In 1890, von Behring and Kitasato succeeded in immunizing guinea pigs with a heat-attenuated toxoid that raised protective antitoxins. Regardless, this modified toxin was found to cause severe local reactions in humans and could not be used as a vaccine. In 1909, Theobald Smith in the US showed that diphtheria toxin neutralized by antitoxin formed a Toxin-Anti-Toxin complex, TAT, that remained immunogenic and eliminated local reactions. TAT sometimes was highly toxic, and secondly toxoid was produced in horse serum which can sensitize some individuals to the serum.