Beyond Thalidomide: Birth defects explained.

Abstract

It was a pleasure to read this outstanding and scholarly monograph, the fruit of Professor Janet McCredie's 30 years' experience in the field. The book puts together beautifully, through clear prosem excellent illustrations and an extensitve bibliography, the story of thalidomide and the spin-offs there from.In the description of the thalidomide epidemic between 1958 and 1961, we are reminded that the malformations were throughout the body; virtually no organ was spared. Thalidomide had the ability to exaggerate naturally occurring malformations and Professor McCredie's driving force over the succeeding years was the hypothesis that if the mode of action of thalidomide could be established, the pathogenesis of other sporadic malformations might also be revealed. Several chapters take us through the pharmacology of thalidomide, its use by tetratologists to induce malformations in laboratory animals and its ability to cause neuropathies. There is also an extensive clinical and radiological investigation of the resultant skeletal malformations.Two chapters remind us of the embryonic neural crest, the precursor to sensory and autonomic nerves, and we are introduced to Professor McCredie's next hypothesis, that the underlying mechanism of congenital malformations is an injury to the neural crest. She presents experimental and pathological evidence to support this hypothesis, and a rational approach to congenital defect syndromes. The hypothesis rests on the acceptance that the normal development of a limb, for example, depends on the trophic influence of the embryonic sensory neurone. We are also shown how neural crest injury might cause defects in other structures such as those which meet in the mid-line, and then affecting cylindrical or solid organs. We then move to neurotropism, whereby growth and repair are dependent upon nerves, especially sensory, and that neuritrophism is quantitative, in that sufficient nerves must be present for growth or regeneration to occur. With regard to limb deficiencies, we are shown that limb buds have a natrual nerve supply which is diminished in limb deficient rabbits who had been fed thalidomide.We are then given an explanation of sclerotomes as skeletal elements supplied by one spinal segmental nerve. Examples of sclerotome subtraction are shown logically to be related to the various limb reductions seen clinically. Other chapters explain multiple malformations and those affecting internal organs. We are left with the firm opinion that the teratogenic effect of thalidomide is due to its neurotoxicity and that further knowledge on malformations is likely to be gained through research into neurotoxicology.