THALIDOMIDE SYNDROME IN RHESUS MONKEYS (MACACA MULATTA)

Three pregnant rhesus monkeys (Macaca mulatto) were treated with 100 mg capsules of thalidomide orally on the following schedules: monkey 184R - days 24, 25, 27 of gestation; monkey 197N - gestational days 27, 28, 29; and monkey 140 R - gestational day 30 only. The fetus from monkey 184 R showed severe phocomelia of all extremities, dislocated shoulder and hip joints, rudimentary digits, micrognathia, a bifid gallbladder, malrotation of the gut and a double right coronary artery. Monkey 197 N’s fetus showed only a missing first toe of the right foot and an extra digit of the left. The fetus from monkey 140 R was normal. Not only is administration during a critical and early time period necessary for the development of severe and complete phocomelia in the Rhesus monkey but an impressively low dosage of the compound is needed to achieve this end. During days 24 to 27 of gestation, either no or very early limb buds are present and treatment during this stage of development results in the full phocomelia syndrome. Later treatment (days 27–29) resulted in only posterior limb anomalies indicating a cephalocaudal gradient of susceptibility. By day 30, still before the appearance of finger rays thalidomide was no longer effective in the one treated animal. Soft tissue malformations, both typical (gut malrotation) and atypical (a double gallbladder rather than an absent one) for thalidomide syndrome in humans were also demonstrated. © 1969 S. Karger AG, Basel.