Beyond Thalidomide

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, a diagnostic radiologist, recognized that there were some clues to a possible answer in the radiographs of thalidomide 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, which had been the current thinking, but indicated primary damage to embryonic sensory nerves (neural crest), 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 embryo. The neural crest theory, however, extends beyond thalidomide and could explain the majority of non-genetic birth defects, anatomically similar to those caused by thalidomide, but hitherto unexplained. Thalidomide was the key that opened the lock to reveal the mechanism underlying many, but not all, congenital malformations - its recent revival as a therapeutic agent adds urgency to the need to clarify its mode of action. Beyond Thalidomide examines the neural crest theory in breadth and depth, incorporating evidence from clinical medicine, radiology, biology, pharmacology, neurology, neuroanatomy and neuropathology. Key publications, some now out of print, are restored to their rightful places in the thalidomide saga and background information is provided to help the general reader gain a better understanding of the sciences involved. It will be of particular interest to those involved with birth defects - obstetricians, neonatologists, paediatricians - and also neurologists, scientists in teratology and developmental biology, and thalidomiders themselves. Book jacket.McCredie, Janet is the author of 'Beyond Thalidomide', published 2007 under ISBN 9781853157417 and ISBN 1853157414.