The effect of single and multiple injections of papain protease into the medullary canal of the tibia was studied in young rabbits. Three or four intramedullary injections of two milligrams of dialyzed papain protease, administered under tourniquet control at intervals of three days, resulted consistently in complete closure of one or both of the epiphyseal plates of the injected bone while sparing the epiphyses of other bones. A moderate disparity of limb length was produced in twelve rabbits followed for seven to thirteen weeks.
Arrest of one or both tibial epiphyseal plates occurred in ten of twelve puppies followed for eight to twelve weeks after receiving intramedullary injections of papain. Almost all of the rabbits and puppies with epiphyseal closure also had tibial deformity. Careful standardization of the enzyme dose was required because excessive quantities of the enzyme produced, on intramedullary injection, epiphyseal separation and necrosis of skin and muscle.