Hesselberg I
Bull World Health Organ. 1972;46(4):503-7.
When a BCG strain is maintained by serial subcultures for several years, a change in its genetic properties may occur spontaneously. Such a change occurred in a strain maintained in the Norwegian State BCG Laboratory for 11 years. When received from Sweden in 1953, the strain was sensitive to the main tuberculostatics. However, in 1964, by mere chance, it was found to have become resistant to isoniazid. An examination of extant samples from the batches of freeze-dried vaccine produced during the period 1953-64 enabled the time and speed of the change to be determined. Although an alteration in drug sensitivity may not be harmful, it could cause a loss in the protective potency of a vaccine in man. It was to safeguard against this danger that the system of serial subcultures was discontinued and the seed lot system adopted, in accordance with WHO requirements.
当卡介苗菌株通过连续传代培养维持数年时，其遗传特性可能会自发发生变化。在挪威国家卡介苗实验室保存了11年的一株菌株就发生了这样的变化。1953年从瑞典收到该菌株时，它对主要的抗结核药物敏感。然而，1964年偶然发现它已对异烟肼产生耐药性。对1953年至1964年期间生产的冻干疫苗批次现存样本的检查，使得能够确定这种变化的时间和速度。虽然药物敏感性的改变可能无害，但它可能导致人用疫苗的保护效力丧失。正是为了防范这种危险，根据世界卫生组织的要求，停止了连续传代培养系统，并采用了种子批系统。
