Beyond Thalidomide: Birth Defects Explained

How do birth defects happen? What goes wrong in the embryo? These perennial questions were brought into sharp focus in the wake of the thalidomide catastrophe (1958-1962). How did thalidomide mutilate the embryo? Despite research efforts, these questions have remained unanswered. The author recognized that there were some clues to a possible answer in the radiographs of thalidomicde children, although these had not been fully analysed. Taking a new approach to the disordered anatomy, she found that the character and the distribution of skeletal defects was inconsistent with primary bone disease but indicated primary damage to embryonic sensory nerves with subsequent failure of formation of bones and joints. Thalidomide is a notorious sensory neurotoxin in adults and her analysis pointed to the same target tissue in the embryuo. The neural crest theory, extends beyond thalidomide and could explain the majority of non-genetic birth defects, anatomically similar to those caused by tahlidomide, but hitherto unexplained. Thalidomide was the key that opened the lock to reveal the mechanism underlying many congenital malformations - its recent revival as a therapeutic agent adds urgency to the need to clarify its mode of action.